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2. Non-syndromic inherited retinal diseases in Poland: Genes, mutations, and phenotypes

Author

Tracewska, A. M., Kocyła-Karczmarewicz, B., Rafalska, A., Murawska, J., Jakubaszko-Jabłónska, J., Rydzanicz, M., Stawiński, P., Ciara, E., Beata S. Lipska-Ziętkiewicz, Khan, M. I., Cremers, F. P. M., Płoski, R., and Chrzanowska, K. H.

Subjects
Adult, Male, Adolescent, Genetic Variation, Infant, Eye Diseases, Hereditary, Middle Aged, eye diseases, Phenotype, Genes, Retinal Diseases, Child, Preschool, Mutation, Prevalence, Humans, Female, Genetic Testing, Poland, Child, Research Article, Aged
Abstract

Purpose Inherited retinal diseases (IRDs), encompassing many clinical entities affecting the retina, are classified as rare disorders. Their extreme heterogeneity made molecular screening in the era before next-generation sequencing (NGS) expensive and time-consuming. Since then, many NGS studies of IRD molecular background have been conducted in Western populations; however, knowledge of the IRD mutational spectrum in Poland is still limited. Until now, there has been almost no comprehensive analysis of this particular population regarding the molecular basis and inheritance of IRDs. Therefore, the purpose of this study was to gain knowledge about the type and prevalence of causative variants in the Polish population. Methods We recruited 190 Polish families with non-syndromic IRDs, including Stargardt disease (STGD), retinitis pigmentosa (RP), cone- and cone-rod dystrophy (CD/CRD), achromatopsia, and congenital stationary night blindness. A pool of molecular inversion probes was used, which targeted 108 genes associated with non-syndromic IRDs known in 2013. We applied filtering for known variants occurring with an allele frequency >0.5% in public and in-house databases, with the exception of variants in ABCA4, when the frequency filter was set to 3.0%. Hypomorphic p.(Asn1868Ile) was added manually. In the case of novel missense or splicing variants, we used in silico prediction software to assess mutation causality. Results We detected causative mutations in 115 of the 190 families with non-syndromic IRD (60.2%). Fifty-nine individuals with STGD, RP, and CD/CRD carried causal variants in ABCA4. Novel single nucleotide variants were found in ABCA4, CEP290, EYS, MAK, and CNGA3. The complex allele c.[1622T>C;3113C>T], p.[Leu541Pro;Ala1038Val] was found in 33 individuals with ABCA4-associated disorders, which makes it the most prevalent allele in the Polish population (17% of all solved cases). Diagnosis was reevaluated in 16 cases. Conclusions Previously, there were no comprehensive reports of IRDs in the Polish population. This study is the first to indicate that the most common IRDs in Poland are ABCA4-associated diseases, regardless of the phenotype. In Polish patients with RP, the second most prevalent causal gene was RHO and the third RPGR, while there were not as many mutations in EYS as in Western populations. The number of initial erroneous diagnoses may be the result of limited access to diagnostics with advanced tools, such as electroretinography; however, it is necessary to raise awareness among Polish ophthalmologists of rare IRDs. Additionally, it must be emphasized that in some cases genetic analysis of the patient is necessary to achieve an accurate diagnosis.

Published
2021

3. The need for widely available genomic testing in rare eye diseases: an ERN-EYE position statement

Author

Black G. C., Sergouniotis P., Sodi A., Leroy B. P., Van Cauwenbergh C., Liskova P., Gronskov K., Klett A., Kohl S., Taurina G., Sukys M., Haer-Wigman L., Nowomiejska K., Marques J. P., Leroux D., Cremers F. P. M., De Baere E., Dollfus H., Ashworth J., Audo I., Bacci G., Balciuniene V. J., Bargiacchi S., Bertelsen M., Black G., Boon C., Bremond-Gignac D., Buzzonetti L., Calvas P., Thomsen A. C., Chirita-Emandi A., Chokoshvili D., Cremers F., Daly A., Downes S., Fasolo A., Fasser C., Fischer D., Fortunato P., Gelzinis A., Hall G., Hamann S., Heon E., Iarossi G., Iberg C., Jouanjan G., Kaariainen H., Kahn K., Keegan D., Laengsfeld M., Leon A., Leroux B., Lorenz B., Maggi R., Mauring L., Melico P., Meunier I., Mohand-Said S., Monterosso C., Morandi P., Parmeggiani F., Passerini I., Pelletier V., Peluso F., Perdomo Y., Rapizzi E., Roos L., Roosing S., Rozet J. -M., Simonelli F., Sowden J., Stingl K., Suppiej A., Testa F., Tracewska A., Traficante G., Valeina S., Wheeler-Schilling T., Yu-Wai-Man P., Zeitz C., Zemaitiene R., Leroux, Dorothée [0000-0002-1412-6611], Apollo - University of Cambridge Repository, Ophthalmology, ANS - Complex Trait Genetics, Black, G. C., Sergouniotis, P., Sodi, A., Leroy, B. P., Van Cauwenbergh, C., Liskova, P., Gronskov, K., Klett, A., Kohl, S., Taurina, G., Sukys, M., Haer-Wigman, L., Nowomiejska, K., Marques, J. P., Leroux, D., Cremers, F. P. M., De Baere, E., Dollfus, H., Ashworth, J., Audo, I., Bacci, G., Balciuniene, V. J., Bargiacchi, S., Bertelsen, M., Black, G., Boon, C., Bremond-Gignac, D., Buzzonetti, L., Calvas, P., Thomsen, A. C., Chirita-Emandi, A., Chokoshvili, D., Cremers, F., Daly, A., Downes, S., Fasolo, A., Fasser, C., Fischer, D., Fortunato, P., Gelzinis, A., Hall, G., Hamann, S., Heon, E., Iarossi, G., Iberg, C., Jouanjan, G., Kaariainen, H., Kahn, K., Keegan, D., Laengsfeld, M., Leon, A., Leroux, B., Lorenz, B., Maggi, R., Mauring, L., Melico, P., Meunier, I., Mohand-Said, S., Monterosso, C., Morandi, P., Parmeggiani, F., Passerini, I., Pelletier, V., Peluso, F., Perdomo, Y., Rapizzi, E., Roos, L., Roosing, S., Rozet, J. -M., Simonelli, F., Sowden, J., Stingl, K., Suppiej, A., Testa, F., Tracewska, A., Traficante, G., Valeina, S., Wheeler-Schilling, T., Yu-Wai-Man, P., Zeitz, C., and Zemaitiene, R.

Subjects
0301 basic medicine, Eye Diseases, lcsh:Medicine, CHILDREN, Position statement, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], MOLECULAR-GENETICS, 0302 clinical medicine, HISTORY, Health care, Medicine and Health Sciences, Genetics(clinical), Pharmacology (medical), Child, Genetics (clinical), medicine.diagnostic_test, General Medicine, Genomics, Europe, TRIALS, ERN-EYE, Rare eye diseases, medicine.symptom, Genetic and genomic testing, Human, medicine.medical_specialty, Visual impairment, LEBER CONGENITAL AMAUROSIS, Socio-culturale, DIAGNOSIS, 03 medical and health sciences, Rare Diseases, medicine, Humans, Genetic Testing, Intensive care medicine, Genetic testing, business.industry, CLINICAL-FEATURES, lcsh:R, Rare eye disease, Eye Disease, Human genetics, Clinical trial, 030104 developmental biology, Genomic, 030221 ophthalmology & optometry, Personalized medicine, business, Rare disease
Abstract

Background Rare Eye Diseases (RED) are the leading cause of visual impairment and blindness for children and young adults in Europe. This heterogeneous group of conditions includes over 900 disorders ranging from relatively prevalent disorders such as retinitis pigmentosa to very rare entities such as developmental eye anomalies. A significant number of patients with RED have an underlying genetic etiology. One of the aims of the European Reference Network for Rare Eye Diseases (ERN–EYE) is to facilitate improvement in diagnosis of RED in European member states. Main body Technological advances have allowed genetic and genomic testing for RED. The outcome of genetic testing allows better understanding of the condition and allows reproductive and therapeutic options. The increase of the number of clinical trials for RED has provided urgency for genetic testing in RED. A survey of countries participating in ERN-EYE demonstrated that the majority are able to access some forms of genomic testing. However, there is significant variability, particularly regarding testing as part of clinical service. Some countries have a well-delineated rare disease pathway and have a national plan for rare diseases combined or not with a national plan for genomics in medicine. In other countries, there is a well-established organization of genetic centres that offer reimbursed genomic testing of RED and other rare diseases. Clinicians often rely upon research-funded laboratories or private companies. Notably, some member states rely on cross-border testing by way of an academic research project. Consequently, many clinicians are either unable to access testing or are confronted with long turnaround times. Overall, while the cost of sequencing has dropped, the cumulative cost of a genomic testing service for populations remains considerable. Importantly, the majority of countries reported healthcare budgets that limit testing. Short conclusion Despite technological advances, critical gaps in genomic testing remain in Europe, especially in smaller countries where no formal genomic testing pathways exist. Even within larger countries, the existing arrangements are insufficient to meet the demand and to ensure access. ERN-EYE promotes access to genetic testing in RED and emphasizes the clinical need and relevance of genetic testing in RED.

Published
2021

4. Exploring the missing heritability in subjects with hearing loss, enlarged vestibular aqueducts, and a single or no pathogenic SLC26A4 variant

Author

Smits, J. J. (Jeroen J.), de Bruijn, S. E. (Suzanne E.), Lanting, C. P. (Cornelis P.), Oostrik, J. (Jaap), O’Gorman, L. (Luke), Mantere, T. (Tuomo), D. C. (DOOFNL Consortium), Cremers, F. P. (Frans P. M.), Roosing, S. (Susanne), Yntema, H. G. (Helger G.), de Vrieze, E. (Erik), Derks, R. (Ronny), Hoischen, A. (Alexander), Pegge, S. A. (Sjoert A. H.), Neveling, K. (Kornelia), Pennings, R. J. (Ronald J. E.), Kremer, H. (Hannie), Smits, J. J. (Jeroen J.), de Bruijn, S. E. (Suzanne E.), Lanting, C. P. (Cornelis P.), Oostrik, J. (Jaap), O’Gorman, L. (Luke), Mantere, T. (Tuomo), D. C. (DOOFNL Consortium), Cremers, F. P. (Frans P. M.), Roosing, S. (Susanne), Yntema, H. G. (Helger G.), de Vrieze, E. (Erik), Derks, R. (Ronny), Hoischen, A. (Alexander), Pegge, S. A. (Sjoert A. H.), Neveling, K. (Kornelia), Pennings, R. J. (Ronald J. E.), and Kremer, H. (Hannie)

Abstract

Pathogenic variants in SLC26A4 have been associated with autosomal recessive hearing loss (arHL) and a unilateral or bilateral enlarged vestibular aqueduct (EVA). SLC26A4 is the second most frequently mutated gene in arHL. Despite the strong genotype–phenotype correlation, a significant part of cases remains genetically unresolved. In this study, we investigated a cohort of 28 Dutch index cases diagnosed with HL in combination with an EVA but without (M0) or with a single (M1) pathogenic variant in SLC26A4. To explore the missing heritability, we first determined the presence of the previously described EVA-associated haplotype (Caucasian EVA (CEVA)), characterized by 12 single nucleotide variants located upstream of SLC26A4. We found this haplotype and a delimited V1-CEVA haplotype to be significantly enriched in our M1 patient cohort (10/16 cases). The CEVA haplotype was also present in two M0 cases (2/12). Short- and long-read whole genome sequencing and optical genome mapping could not prioritize any of the variants present within the CEVA haplotype as the likely pathogenic defect. Short-read whole-genome sequencing of the six M1 cases without this haplotype and the two M0/CEVA cases only revealed previously overlooked or misinterpreted splice-altering SLC26A4 variants in two cases, who are now genetically explained. No deep-intronic or structural variants were identified in any of the M1 subjects. With this study, we have provided important insights that will pave the way for elucidating the missing heritability in M0 and M1 SLC26A4 cases. For pinpointing the pathogenic effect of the CEVA haplotype, additional analyses are required addressing defect(s) at the RNA, protein, or epigenetic level.

Published
2021

15. Targeted next generation sequencing reveals genetic defects underlying inherited retinal disease in Iranian families

Author

Tayebi, N., Akinrinade, O., Muhammad Imran Khan, Hejazifar, A., Dehghani, A., Cremers, F. P. M., and Akhlaghi, M.

Subjects
Adult, Male, Heterozygote, Adolescent, Genotype, genetic structures, lcsh:QH426-470, Gene Expression, Iran, Leber congenital amaurosis, Retina, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Macular Degeneration, All institutes and research themes of the Radboud University Medical Center, parasitic diseases, Humans, cone-rod dystrophy, Child, Eye Proteins, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), lcsh:QH301-705.5, Genetic Association Studies, Homozygote, High-Throughput Nucleotide Sequencing, eye diseases, Pedigree, Stargardt disease, lcsh:Genetics, Phenotype, lcsh:Biology (General), Mutation, Female, Cone-Rod Dystrophies, Retinitis Pigmentosa, Research Article
Abstract

Purpose: Inherited retinal diseases (IRDs) are clinically and genetically heterogeneous showing progressive retinal cell death which results in vision loss. IRDs include a wide spectrum of disorders, such as retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), cone-rod dystrophy (CRD), and Stargardt disease (STGD1). Methods: In this study, we performed targeted next-generation sequencing based on molecular inversion probes (MIPs) that allowed the sequence analysis of 108 IRD-associated genes in 50 Iranian IRD probands. Results: The sequencing and variant filtering led to the identification of putative pathogenic variants in 36 out of 50 (72%) probands. Among 36 unique variants, we identified 20 novel variants in 15 genes. Four out of 36 probands carry compound heterozygous variants, and 32 probands carry homozygous variants. Conclusions: Employing a cost-effective targeted next-generation sequencing procedure, we identified the genetic causes of different retinal disorders in the majority of Iranian families in this study.

Published
2019

16. A nonsense mutation in S-antigen (p.Glu306*) causes Oguchi disease

Author

Waheed, N. K., Qavi, A. H., Malik, S. N., Maria, M., Riaz, M., Cremers, F. P. M., Maleeha Azam, and Qamar, R.

Subjects
Arrestin, Genetics and epigenetic pathways of disease [NCMLS 6], Adolescent, G-Protein-Coupled Receptor Kinase 1, Siblings, DNA Mutational Analysis, Homozygote, Hyperhomocysteinemia, Eye Diseases, Hereditary, Pedigree, Sinus Thrombosis, Intracranial, Codon, Nonsense, Night Blindness, Humans, Lupus Erythematosus, Systemic, Female, Pakistan, Alleles, Methylenetetrahydrofolate Reductase (NADPH2), Research Article
Abstract

Contains fulltext : 110974.pdf (Publisher’s version ) (Open Access) PURPOSE: Genetic studies were performed to identify the causative mutation in a 15-year-old girl diagnosed with congenital stationary night blindness (CSNB) presenting Mizuo-Nakamura phenomenon, a typical Oguchi disease symptom. The patient also had dural sinus thrombosis (DST), thrombocytopenia, and systemic lupus erythematosus (SLE). METHODS: Mutation analysis was done by sequencing two candidate genes, S-antigen (SAG; arrestin 1), associated with Oguchi type 1, and rhodopsin kinase (GRK1), associated with Oguchi type 2. In addition, the C677T variation in the methylenetetrahydrofolate reductase (MTHFR) gene was also screened in the family, to determine its probable association with hyperhomocysteinemia in the patient. RESULTS: Sequencing of the SAG and GRK1 resulted in identifying a novel homozygous nonsense mutation (c.916G>T; p.Glu306*) in SAG, which in unaffected siblings either was present in a heterozygous state or absent. The C677T heterozygous allele in the MTHFR gene was found to be associated with hyperhomocysteinemia in the patient and other family members. CONCLUSIONS: This is the first report of Oguchi type 1 in a Pakistani patient due to a nonsense mutation (c.916G>T; p.Glu306*) in SAG. The neurologic and hematological abnormalities likely are not associated with the SAG variant.

Published
2012

17. Missense mutations at homologous positions in the fourth and fifth laminin A G-like domains of eyes shut homolog cause autosomal recessive retinitis pigmentosa

Author

Muhammad Imran Khan, Collin, R. W. J., Arimadyo, K., Micheal, S., Azam, M., Qureshi, N., Faradz, S. M. H., Den Hollander, A. I., Qamar, R., and Cremers, F. P. M.

Subjects
Adult, Male, Genetics and epigenetic pathways of disease [NCMLS 6], Fundus Oculi, Genetic Linkage, DNA Mutational Analysis, Molecular Sequence Data, Mutation, Missense, Genes, Recessive, Genomic disorders and inherited multi-system disorders [IGMD 3], Chromosome Segregation, Electroretinography, Humans, Family, Amino Acid Sequence, Eye Proteins, Base Sequence, Sequence Homology, Amino Acid, Computational Biology, Middle Aged, Lamin Type A, eye diseases, Pedigree, Protein Structure, Tertiary, Female, Retinitis Pigmentosa, Research Article
Abstract

Contains fulltext : 88951.pdf (Publisher’s version ) (Open Access) PURPOSE: To describe two novel mutations in the eyes shut homolog (EYS) gene in two families with autosomal recessive retinitis pigmentosa (arRP) from Pakistan and Indonesia. METHODS: Genome-wide linkage and homozygosity mapping were performed using single nucleotide polymorphism microarray analysis in affected members of the two arRP families. Sequence analysis was performed to identify genetic changes in protein coding exons of EYS. RESULTS: In the Indonesian and Pakistani families, homozygous regions encompassing the EYS gene at 6q12 were identified, with maximum LOD scores of 1.8 and 3.6, respectively. Novel missense variants in the EYS gene (p.D2767Y and p.D3028Y) were found in the Pakistani and Indonesian families, respectively, that co-segregate with the disease phenotype. Interestingly, the missense variants are located at the same homologous position within the fourth and fifth laminin A G-like domains of EYS. CONCLUSIONS: To date, mostly protein-truncating mutations have been described in EYS, while only few patients have been described with pathogenic compound heterozygous missense mutations. The mutations p.D2767Y and p.D3028Y described in this study affect highly conserved residues at homologous positions in laminin A G-like domains and support the notion that missense mutations in EYS can cause arRP.

Published
2010

18. Development of a genotyping microarray for Usher syndrome

Author

Cremers, F P M, et al, Fleischhauer, J C, Berger, W, University of Zurich, and Cremers, F P M

Subjects
11124 Institute of Medical Molecular Genetics, 2716 Genetics (clinical), 1311 Genetics, 570 Life sciences, biology, 610 Medicine & health
Published
2007

23. Non-syndromic retinitis pigmentosa due to mutations in the mucopolysaccharidosis type IIIC gene, heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT)

Author

Haer-Wigman, L., primary, Newman, H., additional, Leibu, R., additional, Bax, N. M., additional, Baris, H. N., additional, Rizel, L., additional, Banin, E., additional, Massarweh, A., additional, Roosing, S., additional, Lefeber, D. J., additional, Zonneveld-Vrieling, M. N., additional, Isakov, O., additional, Shomron, N., additional, Sharon, D., additional, Den Hollander, A. I., additional, Hoyng, C. B., additional, Cremers, F. P. M., additional, and Ben-Yosef, T., additional

Published
2015
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24. Identification of novel mutations in X-linked retinitis pigmentosa families and implications for diagnostic testing

Author

Neidhardt, J., Glaus, E., Lorenz, B., Netzer, C., Li, Y., Schambeck, M., Wittmer, M., Feil, S., Kirschner-Schwabe, R., Rosenberg, T., Cremers, F. P. M., Bergen, A. A. B., Barthelmes, D., Baraki, H., Fabian Schmid, Tanner, G., Fleischhauer, J., Orth, U., Becker, C., Wegscheider, E., Nürnberg, G., Nürnberg, P., Bolz, H. J., Gal, A., Berger, W., ANS - Amsterdam Neuroscience, and Human Genetics

Subjects
Male, Heterozygote, Polymorphism, Genetic, Genetics and epigenetic pathways of disease [NCMLS 6], Inheritance Patterns, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Genetic Diseases, X-Linked, Exons, eye diseases, Pedigree, GTP-Binding Proteins, Mutation, Humans, Family, Female, Eye Proteins, Retinitis Pigmentosa, Immunity, infection and tissue repair [NCMLS 1], Genes, Dominant, Sequence Deletion, Research Article
Abstract

Contains fulltext : 69886.pdf (Publisher’s version ) (Open Access) PURPOSE: The goal of this study was to identify mutations in X-chromosomal genes associated with retinitis pigmentosa (RP) in patients from Germany, The Netherlands, Denmark, and Switzerland. METHODS: In addition to all coding exons of RP2, exons 1 through 15, 9a, ORF15, 15a and 15b of RPGR were screened for mutations. PCR products were amplified from genomic DNA extracted from blood samples and analyzed by direct sequencing. In one family with apparently dominant inheritance of RP, linkage analysis identified an interval on the X chromosome containing RPGR, and mutation screening revealed a pathogenic variant in this gene. Patients of this family were examined clinically and by X-inactivation studies. RESULTS: This study included 141 RP families with possible X-chromosomal inheritance. In total, we identified 46 families with pathogenic sequence alterations in RPGR and RP2, of which 17 mutations have not been described previously. Two of the novel mutations represent the most 3'-terminal pathogenic sequence variants in RPGR and RP2 reported to date. In exon ORF15 of RPGR, we found eight novel and 14 known mutations. All lead to a disruption of open reading frame. Of the families with suggested X-chromosomal inheritance, 35% showed mutations in ORF15. In addition, we found five novel mutations in other exons of RPGR and four in RP2. Deletions in ORF15 of RPGR were identified in three families in which female carriers showed variable manifestation of the phenotype. Furthermore, an ORF15 mutation was found in an RP patient who additionally carries a 6.4 kbp deletion downstream of the coding region of exon ORF15. We did not identify mutations in 39 sporadic male cases from Switzerland. CONCLUSIONS: RPGR mutations were confirmed to be the most frequent cause of RP in families with an X-chromosomal inheritance pattern. We propose a screening strategy to provide molecular diagnostics in these families.

Published
2007

26. RENAL DEVELOPMENT AND CYSTIC DISEASES

Author

Cabrera-Lopez, C., primary, Ars, E., additional, Marti, T., additional, Harris, P. C., additional, Torra, R., additional, Clerckx, C., additional, Migeon, T., additional, Chen, Z., additional, Ronco, P., additional, Plaisier, E., additional, Lamers, I. J., additional, Van Reeuwijk, J., additional, Azam, M., additional, Boldt, K., additional, Maria, M., additional, Koster-Kamphuis, L., additional, Qamar, R., additional, Ueffing, M., additional, Cremers, F. P., additional, Roepman, R., additional, Arts, H. H., additional, Papizh, S., additional, Dlin, V., additional, Leontieva, I., additional, Tutelman, K., additional, Perrone, R. D., additional, Bae, K. T., additional, Chapman, A. B., additional, Devuyst, O., additional, Gansevoort, R. T., additional, Grantham, J. J., additional, Higashihara, E., additional, Torres, V. E., additional, Sergeyeva, O., additional, Zhou, W., additional, Blais, J. D., additional, Czerwiec, F. S., additional, Liu, F., additional, Liao, Y., additional, Fu, P., additional, Casteleijn, N., additional, Zittema, D., additional, Bakker, S., additional, Boertien, W., additional, Gaillard, C., additional, Meijer, E., additional, Spithoven, E., additional, Struck, J., additional, Gansevoort, R., additional, Robinson, P., additional, McEwan, P., additional, Hadimeri, H., additional, Ong, A. C. M., additional, Orskov, B., additional, Peces, R., additional, Sandford, R., additional, Scolari, F., additional, Walz, G., additional, Cooke, C., additional, O'Reilly, K., additional, Riwanto, M., additional, Kapoor, S., additional, Rodriguez, D., additional, Edenhofer, I., additional, Segerer, S., additional, Wuthrich, R. P., additional, De Rechter, S., additional, Bacchetta, J., additional, Van Dyck, M., additional, Evenepoel, P., additional, De Schepper, J., additional, Levtchenko, E., additional, Mekahli, D., additional, Carr, A., additional, Makin, A., additional, Baker, A., additional, Obeidova, L., additional, Stekrova, J., additional, Seeman, T., additional, Puchmajerova, A., additional, Reiterova, J., additional, Kohoutova, M., additional, Tesar, V., additional, Treille, S., additional, Bailly, J.-M., additional, Guillaume, B., additional, Tuta, L., additional, Stanigut, A., additional, Botea, F., additional, Jo, H. A., additional, Park, H. C., additional, Kim, H., additional, Han, M., additional, Huh, H., additional, Jeong, J. C., additional, Oh, K.-H., additional, Yang, J., additional, Koo, T. Y., additional, Hwang, Y.-H., additional, Ahn, C., additional, Pisani, A., additional, Remuzzi, G., additional, Ruggenenti, P., additional, Riccio, E., additional, Visciano, B., additional, Spinelli, L., additional, Kim, J. I., additional, Park, K. M., additional, Liu, F. X., additional, Rutherford, P., additional, Smoyer-Tomic, K., additional, Martinez Jimenez, V., additional, Comas, J., additional, Arcos, E., additional, Diaz, J. M., additional, Muray, S., additional, Cabezuelo, J., additional, Ballarin, J., additional, Miyaoka, T., additional, Morimoto, S., additional, Kataoka, H., additional, Mochizuki, T., additional, Tsuchiya, K., additional, Ichihara, A., additional, and Nitta, K., additional

Published
2014
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27. Genotyping Microarray for CSNB-Associated Genes

Author

Zeitz, C, Labs, S, Lorenz, B, Forster, U, Üksti, J, Kroes, H Y, De Baere, E, Leroy, B P, Cremers, F P M, Wittmer, M, van Genderen, M M, Sahel, J A, Audo, I, Poloschek, C M, Mohand-Said, S, Fleischhauer, J C, Hüffmeier, U, Moskova-Doumanova, V, Levin, A V, Hamel, C P, Leifert, D, Munier, F L, Schorderet, D F, Zrenner, E, Friedburg, C, Wissinger, B, Kohl, S, Berger, W, Zeitz, C, Labs, S, Lorenz, B, Forster, U, Üksti, J, Kroes, H Y, De Baere, E, Leroy, B P, Cremers, F P M, Wittmer, M, van Genderen, M M, Sahel, J A, Audo, I, Poloschek, C M, Mohand-Said, S, Fleischhauer, J C, Hüffmeier, U, Moskova-Doumanova, V, Levin, A V, Hamel, C P, Leifert, D, Munier, F L, Schorderet, D F, Zrenner, E, Friedburg, C, Wissinger, B, Kohl, S, and Berger, W

Abstract

PURPOSE. Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous retinal disease. Although electroretinographic (ERG) measurements can discriminate clinical subgroups, the identification of the underlying genetic defects has been complicated for CSNB because ofgenetic heterogeneity, the uncertainty about the mode of inheritance, and time-consuming and costly mutation scanning and direct sequencing approaches. METHODS. To overcome these challenges and to generate a time- and cost-efficient mutation screening tool, the authors developed a CSNB genotyping microarray with arrayed primer extension (APEX) technology. To cover as many mutations as possible, a comprehensive literature search was performed, and DNA samples from a cohort of patients with CSNB were first sequenced directly in known CSNB genes. Subsequently, oligonucleotides were designed representing 126 sequence variations in RHO, CABP4, CACNA1F, CACNA2D4, GNAT1,GRM6, NYX, PDE6B, and SAG and spotted on the chip. RESULTS. Direct sequencing of genes known to be associated with CSNB in the study cohort revealed 21 mutations (12 novel and 9 previously reported). The resultant microarray containing oligonucleotides, which allow to detect 126 known and novel mutations, was 100% effective in determining the expected sequence changes in all known samples assessed. In addition, investigation of 34 patients with CSNB who were previously not genotyped revealed sequence variants in 18%, of which 15% are thought to be disease-causing mutations. CONCLUSIONS. This relatively inexpensive first-pass genetic testing device for patients with a diagnosis of CSNB will improve molecular diagnostics and genetic counseling of patients and their families and gives the opportunity to analyze whether, for example, more progressive disorders such as cone or cone–rod dystrophies underlie the same gene defects.

Published
2009

30. Detection and characterization of point mutations in the choroideremia candidate gene by PCR-SSCP analysis and direct DNA sequencing

Author

van den Hurk, J. A. J. M., van de Pol, T. J. R., Molloy, C. M., Brunsmann, F., Rüther, K., Zrenner, E., Pinckers, A. J. L. G., Pawlowitzki, I. H., Bleeker-Wagemakers, E. M., Wieringa, B., Ropers, H. -H., and Cremers, F. P. M.

Subjects
X Chromosome, Base Sequence, Choroid, Molecular Sequence Data, Chromosome Mapping, DNA, Single-Stranded, Original Articles, DNA, Exons, Polymerase Chain Reaction, eye diseases, Retina, Translocation, Genetic, Chromosome Banding, Open Reading Frames, Genes, Oligodeoxyribonucleotides, Mutation, Humans, Female, sense organs, Amino Acid Sequence, Chromosome Deletion, Pigment Epithelium of Eye, Choroideremia
Abstract

By making use of positional cloning strategies we recently isolated a candidate gene for choroideremia (CHM), which is transcribed in retina, choroid, and/or retinal pigment epithelium. The gene contains an open reading frame that is structurally altered in 10 CHM patients with sizable deletions and in a female patient with a balanced translocation involving the Xq21 band. Employing PCR-SSCP analysis and direct DNA sequencing we have now detected and characterized different point mutations in five patients with CHM. Each of these mutations introduces a termination codon into the open reading frame of the CHM candidate gene, thereby predicting a distinct truncated protein product. Together these findings provide convincing evidence for the candidate gene being identical with the choroideremia gene.

Published
1992

32. Development of a genotyping microarray for Usher syndrome

Author

Cremers, F. P M, primary, Kimberling, W. J, additional, Kulm, M., additional, de Brouwer, A. P, additional, van Wijk, E., additional, te Brinke, H., additional, Cremers, C. W R J, additional, Hoefsloot, L. H, additional, Banfi, S., additional, Simonelli, F., additional, Fleischhauer, J. C, additional, Berger, W., additional, Kelley, P. M, additional, Haralambous, E., additional, Bitner-Glindzicz, M., additional, Webster, A. R, additional, Saihan, Z., additional, De Baere, E., additional, Leroy, B. P, additional, Silvestri, G., additional, McKay, G. J, additional, Koenekoop, R. K, additional, Millan, J. M, additional, Rosenberg, T., additional, Joensuu, T., additional, Sankila, E.-M., additional, Weil, D., additional, Weston, M. D, additional, Wissinger, B., additional, and Kremer, H., additional

Published
2006
Full Text
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34. A common ancestor for COCH related cochleovestibular (DFNA9) patients in Belgium and The Netherlands bearing the P51S mutation

Author

FRANSEN, E., primary, VERSTREKEN, M., additional, BOM, S. J. H., additional, LEMAIRE, F., additional, KEMPERMAN, M. H., additional, DE KOK, Y. J. M., additional, WUYTS, F. L., additional, VERHAGEN, W. I. M., additional, HUYGEN, P. L. M., additional, MCGUIRT, W. T., additional, SMITH, R. J. H., additional, VAN MALDERGEM, L., additional, DECLAU, F., additional, CREMERS, C. W. R. J., additional, VAN DE HEYNING, P. H., additional, CREMERS, F. P. M., additional, and VAN CAMP, G., additional

Published
2001
Full Text
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35. Human genome meeting 2016

Author

Srivastava, A., Wang, Y., Huang, R., Skinner, C., Thompson, T., Pollard, L., Wood, T., Luo, F., Stevenson, R., Polimanti, R., Gelernter, J., Lin, X., Lim, I., Wu, Y., Teh, A., Chen, L., Aris, I., Soh, S., Tint, M., MacIsaac, J., Yap, F., Kwek, K., Saw, S., Kobor, M., Meaney, M., Godfrey, K., Chong, Y., Holbrook, J., Lee, Y., Gluckman, P., Karnani, N., Kapoor, A., Lee, D., Chakravarti, A., Maercker, C., Graf, F., Boutros, M., Stamoulis, G., Santoni, F., Makrythanasis, P., Letourneau, A., Guipponi, M., Panousis, N., Garieri, M., Ribaux, P., Falconnet, E., Borel, C., Antonarakis, S., Kumar, S., Curran, J., Blangero, J., Chatterjee, S., Kapoor, A., Akiyama, J., Auer, D., Berrios, C., Pennacchio, L., Chakravarti, A., Donti, T., Cappuccio, G., Miller, M., Atwal, P., Kennedy, A., Cardon, A., Bacino, C., Emrick, L., Hertecant, J., Baumer, F., Porter, B., Bainbridge, M., Bonnen, P., Graham, B., Sutton, R., Sun, Q., Elsea, S., Hu, Z., Wang, P., Zhu, Y., Zhao, J., Xiong, M., Bennett, David, Hidalgo-Miranda, A., Romero-Cordoba, S., Rodriguez-Cuevas, S., Rebollar-Vega, R., Tagliabue, E., Iorio, M., D’Ippolito, E., Baroni, S., Kaczkowski, B., Tanaka, Y., Kawaji, H., Sandelin, A., Andersson, R., Itoh, M., Lassmann, T., Hayashizaki, Y., Carninci, P., Forrest, A., Semple, C., Rosenthal, E., Shirts, B., Amendola, L., Gallego, C., Horike-Pyne, M., Burt, A., Robertson, P., Beyers, P., Nefcy, C., Veenstra, D., Hisama, F., Bennett, R., Dorschner, M., Nickerson, D., Smith, J., Patterson, K., Crosslin, D., Nassir, R., Zubair, N., Harrison, T., Peters, U., Jarvik, G., Menghi, F., Inaki, K., Woo, X., Kumar, P., Grzeda, K., Malhotra, A., Kim, H., Ucar, D., Shreckengast, P., Karuturi, K., Keck, J., Chuang, J., Liu, E., Ji, B., Tyler, A., Ananda, G., Carter, G., Nikbakht, H., Montagne, M., Zeinieh, M., Harutyunyan, A., Mcconechy, M., Jabado, N., Lavigne, P., Majewski, J., Goldstein, J., Overman, M., Varadhachary, G., Shroff, R., Wolff, R., Javle, M., Futreal, A., Fogelman, D., Bravo, L., Fajardo, W., Gomez, H., Castaneda, C., Rolfo, C., Pinto, J., Akdemir, K., Chin, L., Futreal, A., Patterson, S., Statz, C., Mockus, S., Nikolaev, S., Bonilla, X., Parmentier, L., King, B., Bezrukov, F., Kaya, G., Zoete, V., Seplyarskiy, V., Sharpe, H., McKee, T., Letourneau, A., Ribaux, P., Popadin, K., Basset-Seguin, N., Chaabene, R., Santoni, F., Andrianova, M., Guipponi, M., Garieri, M., Verdan, C., Grosdemange, K., Sumara, O., Eilers, M., Aifantis, I., Michielin, O., de Sauvage, F., Antonarakis, S., Likhitrattanapisal, S., Lincoln, S., Kurian, A., Desmond, A., Yang, S., Kobayashi, Y., Ford, J., Ellisen, L., Peters, T., Alvarez, K., Hollingsworth, E., Lopez-Terrada, D., Hastie, A., Dzakula, Z., Pang, A., Lam, E., Anantharaman, T., Saghbini, M., Cao, H., Gonzaga-Jauregui, C., Ma, L., King, A., Rosenzweig, E., Krishnan, U., Reid, J., Overton, J., Dewey, F., Chung, W., Small, K., DeLuca, A., Cremers, F., Lewis, R., Puech, V., Bakall, B., Silva-Garcia, R., Rohrschneider, K., Leys, M., Shaya, F., Stone, E., Sobreira, N., Schiettecatte, F., Ling, H., Pugh, E., Witmer, D., Hetrick, K., Zhang, P., Doheny, K., Valle, D., Hamosh, A., Jhangiani, S., Akdemir, Z., Bainbridge, M., Charng, W., Wiszniewski, W., Gambin, T., Karaca, E., Bayram, Y., Eldomery, M., Posey, J., Doddapaneni, H., Hu, J., Sutton, V., Muzny, D., Boerwinkle, E., Valle, D., Lupski, J., Gibbs, R., Shekar, S., Salerno, W., English, A., Mangubat, A., Bruestle, J., Thorogood, A., Knoppers, B., Takahashi, H., Nitta, K., Kozhuharova, A., Suzuki, A., Sharma, H., Cotella, D., Santoro, C., Zucchelli, S., Gustincich, S., Carninci, P., Mulvihill, J., Baynam, G., Gahl, W., Groft, S., Kosaki, K., Lasko, P., Melegh, B., Taruscio, D., Ghosh, R., Plon, S., Scherer, S., Qin, X., Sanghvi, R., Walker, K., Chiang, T., Muzny, D., Wang, L., Black, J., Boerwinkle, E., Weinshilboum, R., Gibbs, R., Karpinets, T., Calderone, T., Wani, K., Yu, X., Creasy, C., Haymaker, C., Forget, M., Nanda, V., Roszik, J., Wargo, J., Haydu, L., Song, X., Lazar, A., Gershenwald, J., Davies, M., Bernatchez, C., Zhang, J., Futreal, A., Woodman, S., Chesler, E., Reynolds, T., Bubier, J., Phillips, C., Langston, M., Baker, E., Xiong, M., Ma, L., Lin, N., Amos, C., Lin, N., Wang, P., Zhu, Y., Zhao, J., Calhoun, V., Xiong, M., Dobretsberger, O., Egger, M., Leimgruber, F., Sadedin, S., Oshlack, A., Antonio, V., Ono, N., Ahmed, Z., Bolisetty, M., Zeeshan, S., Anguiano, E., Ucar, D., Sarkar, A., Nandineni, M., Zeng, C., Shao, J., Cao, H., Hastie, A., Pang, A., Lam, E., Liang, T., Pham, K., Saghbini, M., Dzakula, Z., Chee-Wei, Y., Dongsheng, L., Lai-Ping, W., Lian, D., Hee, R., Yunus, Y., Aghakhanian, F., Mokhtar, S., Lok-Yung, C., Bhak, J., Phipps, M., Shuhua, X., Yik-Ying, T., Kumar, V., Boon-Peng, H., Campbell, I., Young, M., James, P., Rain, M., Mohammad, G., Kukreti, R., Pasha, Q., Akilzhanova, A., Guelly, C., Abilova, Z., Rakhimova, S., Akhmetova, A., Kairov, U., Trajanoski, S., Zhumadilov, Z., Bekbossynova, M., Schumacher, C., Sandhu, S., Harkins, T., Makarov, V., Doddapaneni, H., Glenn, R., Momin, Z., Dilrukshi, B., Chao, H., Meng, Q., Gudenkauf, B., Kshitij, R., Jayaseelan, J., Nessner, C., Lee, S., Blankenberg, K., Lewis, L., Hu, J., Han, Y., Dinh, H., Jireh, S., Walker, K., Boerwinkle, E., Muzny, D., Gibbs, R., Hu, J., Walker, K., Buhay, C., Liu, X., Wang, Q., Sanghvi, R., Doddapaneni, H., Ding, Y., Veeraraghavan, N., Yang, Y., Boerwinkle, E., Beaudet, A., Eng, C., Muzny, D., Gibbs, R., Worley, K., Liu, Y., Hughes, D., Murali, S., Harris, R., English, A., Qin, X., Hampton, O., Larsen, P., Beck, C., Han, Y., Wang, M., Doddapaneni, H., Kovar, C., Salerno, W., Yoder, A., Richards, S., Rogers, J., Lupski, J., Muzny, D., Gibbs, R., Meng, Q., Bainbridge, M., Wang, M., Doddapaneni, H., Han, Y., Muzny, D., Gibbs, R., Harris, R., Raveenedran, M., Xue, C., Dahdouli, M., Cox, L., Fan, G., Ferguson, B., Hovarth, J., Johnson, Z., Kanthaswamy, S., Kubisch, M., Platt, M., Smith, D., Vallender, E., Wiseman, R., Liu, X., Below, J., Muzny, D., Gibbs, R., Yu, F., Rogers, J., Lin, J., Zhang, Y., Ouyang, Z., Moore, A., Wang, Z., Hofmann, J., Purdue, M., Stolzenberg-Solomon, R., Weinstein, S., Albanes, D., Liu, C., Cheng, W., Lin, T., Lan, Q., Rothman, N., Berndt, S., Chen, E., Bahrami, H., Khoshzaban, A., Keshal, S., Bahrami, H., Khoshzaban, A., Keshal, S., Alharbi, K., Zhalbinova, M., Akilzhanova, A., Rakhimova, S., Bekbosynova, M., Myrzakhmetova, S., Matar, M., Mili, N., Molinari, R., Ma, Y., Guerrier, S., Elhawary, N., Tayeb, M., Bogari, N., Qotb, N., McClymont, S., Hook, P., Goff, L., McCallion, A., Kong, Y., Charette, J., Hicks, W., Naggert, J., Zhao, L., Nishina, P., Edrees, B., Athar, M., Al-Allaf, F., Taher, M., Khan, W., Bouazzaoui, A., Harbi, N., Safar, R., Al-Edressi, H., Anazi, A., Altayeb, N., Ahmed, M., Alansary, K., Abduljaleel, Z., Kratz, A., Beguin, P., Poulain, S., Kaneko, M., Takahiko, C., Matsunaga, A., Kato, S., Suzuki, A., Bertin, N., Lassmann, T., Vigot, R., Carninci, P., Plessy, C., Launey, T., Graur, D., Lee, D., Kapoor, A., Chakravarti, A., Friis-Nielsen, J., Izarzugaza, J., Brunak, S., Chakraborty, A., Basak, J., Mukhopadhyay, A., Soibam, B., Das, D., Biswas, N., Das, S., Sarkar, S., Maitra, A., Panda, C., Majumder, P., Morsy, H., Gaballah, A., Samir, M., Shamseya, M., Mahrous, H., Ghazal, A., Arafat, W., Hashish, M., Gruber, J., Jaeger, N., Snyder, M., Patel, K., Bowman, S., Davis, T., Kraushaar, D., Emerman, A., Russello, S., Henig, N., Hendrickson, C., Zhang, K., Rodriguez-Dorantes, M., Cruz-Hernandez, C., Garcia-Tobilla, C., Solorzano-Rosales, S., Jäger, N., Chen, J., Haile, R., Hitchins, M., Brooks, J., Snyder, M., Jiménez-Morales, S., Ramírez, M., Nuñez, J., Bekker, V., Leal, Y., Jiménez, E., Medina, A., Hidalgo, A., Mejía, J., Halytskiy, V., Naggert, J., Collin, G., DeMauro, K., Hanusek, R., Nishina, P., Belhassa, K., Belhassan, K., Bouguenouch, L., Samri, I., Sayel, H., moufid, FZ., El Bouchikhi, I., Trhanint, S., Hamdaoui, H., Elotmani, I., Khtiri, I., Kettani, O., Quibibo, L., Ahagoud, M., Abbassi, M., Ouldim, K., Marusin, A., Kornetov, A., Swarovskaya, M., Vagaiceva, K., Stepanov, V., De La Paz, E., Sy, R., Nevado, J., Reganit, P., Santos, L., Magno, J., Punzalan, F., Ona, D., Llanes, E., Santos-Cortes, R., Tiongco, R., Aherrera, J., Abrahan, L., Pagauitan-Alan, P., Morelli, K., Domire, J., Pyne, N., Harper, S., Burgess, R., Zhalbinova, M., Akilzhanova, A., Rakhimova, S., Bekbosynova, M., Myrzakhmetova, S., Gari, M., Dallol, A., Alsehli, H., Gari, A., Gari, M., Abuzenadah, A., Thomas, M., Sukhai, M., Garg, S., Misyura, M., Zhang, T., Schuh, A., Stockley, T., Kamel-Reid, S., Sherry, S., Xiao, C., Slotta, D., Rodarmer, K., Feolo, M., Kimelman, M., Godynskiy, G., O’Sullivan, C., Yaschenko, E., Xiao, C., Yaschenko, E., Sherry, S., Rangel-Escareño, C., Rueda-Zarate, H., Tayubi, I., Mohammed, R., Ahmed, I., Ahmed, T., Seth, S., Amin, S., Song, X., Mao, X., Sun, H., Verhaak, R., Futreal, A., Zhang, J., Whiite, S., Chiang, T., English, A., Farek, J., Kahn, Z., Salerno, W., Veeraraghavan, N., Boerwinkle, E., Gibbs, R., Kasukawa, T., Lizio, M., Harshbarger, J., Hisashi, S., Severin, J., Imad, A., Sahin, S., Freeman, T., Baillie, K., Sandelin, A., Carninci, P., Forrest, A., Kawaji, H., Salerno, W., English, A., Shekar, S., Mangubat, A., Bruestle, J., Boerwinkle, E., Gibbs, R., Salem, A., Ali, M., Ibrahim, A., Ibrahim, M., Barrera, H., Garza, L., Torres, J., Barajas, V., Ulloa-Aguirre, A., Kershenobich, D., Mortaji, Shahroj, Guizar, Pedro, Loera, Eliezer, Moreno, Karen, De León, Adriana, Monsiváis, Daniela, Gómez, Jackeline, Cardiel, Raquel, Fernandez-Lopez, J., Bonifaz-Peña, V., Rangel-Escareño, C., Hidalgo-Miranda, A., Contreras, A., Polfus, L., Wang, X., Philip, V., Carter, G., Abuzenadah, A., Gari, M., Turki, R., Dallol, A., Uyar, A., Kaygun, A., Zaman, S., Marquez, E., George, J., Ucar, D., Hendrickson, C., Emerman, A., Kraushaar, D., Bowman, S., Henig, N., Davis, T., Russello, S., Patel, K., Starr, D., Baird, M., Kirkpatrick, B., Sheets, K., Nitsche, R., Prieto-Lafuente, L., Landrum, M., Lee, J., Rubinstein, W., Maglott, D., Thavanati, P., de Dios, A., Hernandez, R., Aldrate, M., Mejia, M., Kanala, K., Abduljaleel, Z., Khan, W., Al-Allaf, F., Athar, M., Taher, M., Shahzad, N., Bouazzaoui, A., Huber, E., Dan, A., Al-Allaf, F., Herr, W., Sprotte, G., Köstler, J., Hiergeist, A., Gessner, A., Andreesen, R., Holler, E., Al-Allaf, F., Alashwal, A., Abduljaleel, Z., Taher, M., Bouazzaoui, A., Abalkhail, H., Al-Allaf, A., Bamardadh, R., Athar, M., Filiptsova, O., Kobets, M., Kobets, Y., Burlaka, I., Timoshyna, I., Filiptsova, O., Kobets, M., Kobets, Y., Burlaka, I., Timoshyna, I., Filiptsova, O., Kobets, M., Kobets, Y., Burlaka, I., Timoshyna, I., Al-allaf, F., Mohiuddin, M., Zainularifeen, A., Mohammed, A., Abalkhail, H., Owaidah, T., and Bouazzaoui, A.

Abstract

O1 The metabolomics approach to autism: identification of biomarkers for early detection of autism spectrum disorder A. K. Srivastava, Y. Wang, R. Huang, C. Skinner, T. Thompson, L. Pollard, T. Wood, F. Luo, R. Stevenson O2 Phenome-wide association study for smoking- and drinking-associated genes in 26,394 American women with African, Asian, European, and Hispanic descents R. Polimanti, J. Gelernter O3 Effects of prenatal environment, genotype and DNA methylation on birth weight and subsequent postnatal outcomes: findings from GUSTO, an Asian birth cohort X. Lin, I. Y. Lim, Y. Wu, A. L. Teh, L. Chen, I. M. Aris, S. E. Soh, M. T. Tint, J. L. MacIsaac, F. Yap, K. Kwek, S. M. Saw, M. S. Kobor, M. J. Meaney, K. M. Godfrey, Y. S. Chong, J. D. Holbrook, Y. S. Lee, P. D. Gluckman, N. Karnani, GUSTO study group O4 High-throughput identification of specific qt interval modulating enhancers at the SCN5A locus A. Kapoor, D. Lee, A. Chakravarti O5 Identification of extracellular matrix components inducing cancer cell migration in the supernatant of cultivated mesenchymal stem cells C. Maercker, F. Graf, M. Boutros O6 Single cell allele specific expression (ASE) IN T21 and common trisomies: a novel approach to understand DOWN syndrome and other aneuploidies G. Stamoulis, F. Santoni, P. Makrythanasis, A. Letourneau, M. Guipponi, N. Panousis, M. Garieri, P. Ribaux, E. Falconnet, C. Borel, S. E. Antonarakis O7 Role of microRNA in LCL to IPSC reprogramming S. Kumar, J. Curran, J. Blangero O8 Multiple enhancer variants disrupt gene regulatory network in Hirschsprung disease S. Chatterjee, A. Kapoor, J. Akiyama, D. Auer, C. Berrios, L. Pennacchio, A. Chakravarti O9 Metabolomic profiling for the diagnosis of neurometabolic disorders T. R. Donti, G. Cappuccio, M. Miller, P. Atwal, A. Kennedy, A. Cardon, C. Bacino, L. Emrick, J. Hertecant, F. Baumer, B. Porter, M. Bainbridge, P. Bonnen, B. Graham, R. Sutton, Q. Sun, S. Elsea O10 A novel causal methylation network approach to Alzheimer’s disease Z. Hu, P. Wang, Y. Zhu, J. Zhao, M. Xiong, David A Bennett O11 A microRNA signature identifies subtypes of triple-negative breast cancer and reveals MIR-342-3P as regulator of a lactate metabolic pathway A. Hidalgo-Miranda, S. Romero-Cordoba, S. Rodriguez-Cuevas, R. Rebollar-Vega, E. Tagliabue, M. Iorio, E. D’Ippolito, S. Baroni O12 Transcriptome analysis identifies genes, enhancer RNAs and repetitive elements that are recurrently deregulated across multiple cancer types B. Kaczkowski, Y. Tanaka, H. Kawaji, A. Sandelin, R. Andersson, M. Itoh, T. Lassmann, the FANTOM5 consortium, Y. Hayashizaki, P. Carninci, A. R. R. Forrest O13 Elevated mutation and widespread loss of constraint at regulatory and architectural binding sites across 11 tumour types C. A. Semple O14 Exome sequencing provides evidence of pathogenicity for genes implicated in colorectal cancer E. A. Rosenthal, B. Shirts, L. Amendola, C. Gallego, M. Horike-Pyne, A. Burt, P. Robertson, P. Beyers, C. Nefcy, D. Veenstra, F. Hisama, R. Bennett, M. Dorschner, D. Nickerson, J. Smith, K. Patterson, D. Crosslin, R. Nassir, N. Zubair, T. Harrison, U. Peters, G. Jarvik, NHLBI GO Exome Sequencing Project O15 The tandem duplicator phenotype as a distinct genomic configuration in cancer F. Menghi, K. Inaki, X. Woo, P. Kumar, K. Grzeda, A. Malhotra, H. Kim, D. Ucar, P. Shreckengast, K. Karuturi, J. Keck, J. Chuang, E. T. Liu O16 Modeling genetic interactions associated with molecular subtypes of breast cancer B. Ji, A. Tyler, G. Ananda, G. Carter O17 Recurrent somatic mutation in the MYC associated factor X in brain tumors H. Nikbakht, M. Montagne, M. Zeinieh, A. Harutyunyan, M. Mcconechy, N. Jabado, P. Lavigne, J. Majewski O18 Predictive biomarkers to metastatic pancreatic cancer treatment J. B. Goldstein, M. Overman, G. Varadhachary, R. Shroff, R. Wolff, M. Javle, A. Futreal, D. Fogelman O19 DDIT4 gene expression as a prognostic marker in several malignant tumors L. Bravo, W. Fajardo, H. Gomez, C. Castaneda, C. Rolfo, J. A. Pinto O20 Spatial organization of the genome and genomic alterations in human cancers K. C. Akdemir, L. Chin, A. Futreal, ICGC PCAWG Structural Alterations Group O21 Landscape of targeted therapies in solid tumors S. Patterson, C. Statz, S. Mockus O22 Genomic analysis reveals novel drivers and progression pathways in skin basal cell carcinoma S. N. Nikolaev, X. I. Bonilla, L. Parmentier, B. King, F. Bezrukov, G. Kaya, V. Zoete, V. Seplyarskiy, H. Sharpe, T. McKee, A. Letourneau, P. Ribaux, K. Popadin, N. Basset-Seguin, R. Ben Chaabene, F. Santoni, M. Andrianova, M. Guipponi, M. Garieri, C. Verdan, K. Grosdemange, O. Sumara, M. Eilers, I. Aifantis, O. Michielin, F. de Sauvage, S. Antonarakis O23 Identification of differential biomarkers of hepatocellular carcinoma and cholangiocarcinoma via transcriptome microarray meta-analysis S. Likhitrattanapisal O24 Clinical validity and actionability of multigene tests for hereditary cancers in a large multi-center study S. Lincoln, A. Kurian, A. Desmond, S. Yang, Y. Kobayashi, J. Ford, L. Ellisen O25 Correlation with tumor ploidy status is essential for correct determination of genome-wide copy number changes by SNP array T. L. Peters, K. R. Alvarez, E. F. Hollingsworth, D. H. Lopez-Terrada O26 Nanochannel based next-generation mapping for interrogation of clinically relevant structural variation A. Hastie, Z. Dzakula, A. W. Pang, E. T. Lam, T. Anantharaman, M. Saghbini, H. Cao, BioNano Genomics O27 Mutation spectrum in a pulmonary arterial hypertension (PAH) cohort and identification of associated truncating mutations in TBX4 C. Gonzaga-Jauregui, L. Ma, A. King, E. Berman Rosenzweig, U. Krishnan, J. G. Reid, J. D. Overton, F. Dewey, W. K. Chung O28 NORTH CAROLINA macular dystrophy (MCDR1): mutations found affecting PRDM13 K. Small, A. DeLuca, F. Cremers, R. A. Lewis, V. Puech, B. Bakall, R. Silva-Garcia, K. Rohrschneider, M. Leys, F. S. Shaya, E. Stone O29 PhenoDB and genematcher, solving unsolved whole exome sequencing data N. L. Sobreira, F. Schiettecatte, H. Ling, E. Pugh, D. Witmer, K. Hetrick, P. Zhang, K. Doheny, D. Valle, A. Hamosh O30 Baylor-Johns Hopkins Center for Mendelian genomics: a four year review S. N. Jhangiani, Z. Coban Akdemir, M. N. Bainbridge, W. Charng, W. Wiszniewski, T. Gambin, E. Karaca, Y. Bayram, M. K. Eldomery, J. Posey, H. Doddapaneni, J. Hu, V. R. Sutton, D. M. Muzny, E. A. Boerwinkle, D. Valle, J. R. Lupski, R. A. Gibbs O31 Using read overlap assembly to accurately identify structural genetic differences in an ashkenazi jewish trio S. Shekar, W. Salerno, A. English, A. Mangubat, J. Bruestle O32 Legal interoperability: a sine qua non for international data sharing A. Thorogood, B. M. Knoppers, Global Alliance for Genomics and Health - Regulatory and Ethics Working Group O33 High throughput screening platform of competent sineups: that can enhance translation activities of therapeutic target H. Takahashi, K. R. Nitta, A. Kozhuharova, A. M. Suzuki, H. Sharma, D. Cotella, C. Santoro, S. Zucchelli, S. Gustincich, P. Carninci O34 The undiagnosed diseases network international (UDNI): clinical and laboratory research to meet patient needs J. J. Mulvihill, G. Baynam, W. Gahl, S. C. Groft, K. Kosaki, P. Lasko, B. Melegh, D. Taruscio O36 Performance of computational algorithms in pathogenicity predictions for activating variants in oncogenes versus loss of function mutations in tumor suppressor genes R. Ghosh, S. Plon O37 Identification and electronic health record incorporation of clinically actionable pharmacogenomic variants using prospective targeted sequencing S. Scherer, X. Qin, R. Sanghvi, K. Walker, T. Chiang, D. Muzny, L. Wang, J. Black, E. Boerwinkle, R. Weinshilboum, R. Gibbs O38 Melanoma reprogramming state correlates with response to CTLA-4 blockade in metastatic melanoma T. Karpinets, T. Calderone, K. Wani, X. Yu, C. Creasy, C. Haymaker, M. Forget, V. Nanda, J. Roszik, J. Wargo, L. Haydu, X. Song, A. Lazar, J. Gershenwald, M. Davies, C. Bernatchez, J. Zhang, A. Futreal, S. Woodman O39 Data-driven refinement of complex disease classification from integration of heterogeneous functional genomics data in GeneWeaver E. J. Chesler, T. Reynolds, J. A. Bubier, C. Phillips, M. A. Langston, E. J. Baker O40 A general statistic framework for genome-based disease risk prediction M. Xiong, L. Ma, N. Lin, C. Amos O41 Integrative large-scale causal network analysis of imaging and genomic data and its application in schizophrenia studies N. Lin, P. Wang, Y. Zhu, J. Zhao, V. Calhoun, M. Xiong O42 Big data and NGS data analysis: the cloud to the rescue O. Dobretsberger, M. Egger, F. Leimgruber O43 Cpipe: a convergent clinical exome pipeline specialised for targeted sequencing S. Sadedin, A. Oshlack, Melbourne Genomics Health Alliance O44 A Bayesian classification of biomedical images using feature extraction from deep neural networks implemented on lung cancer data V. A. A. Antonio, N. Ono, Clark Kendrick C. Go O45 MAV-SEQ: an interactive platform for the Management, Analysis, and Visualization of sequence data Z. Ahmed, M. Bolisetty, S. Zeeshan, E. Anguiano, D. Ucar O47 Allele specific enhancer in EPAS1 intronic regions may contribute to high altitude adaptation of Tibetans C. Zeng, J. Shao O48 Nanochannel based next-generation mapping for structural variation detection and comparison in trios and populations H. Cao, A. Hastie, A. W. Pang, E. T. Lam, T. Liang, K. Pham, M. Saghbini, Z. Dzakula O49 Archaic introgression in indigenous populations of Malaysia revealed by whole genome sequencing Y. Chee-Wei, L. Dongsheng, W. Lai-Ping, D. Lian, R. O. Twee Hee, Y. Yunus, F. Aghakhanian, S. S. Mokhtar, C. V. Lok-Yung, J. Bhak, M. Phipps, X. Shuhua, T. Yik-Ying, V. Kumar, H. Boon-Peng O50 Breast and ovarian cancer prevention: is it time for population-based mutation screening of high risk genes? I. Campbell, M.-A. Young, P. James, Lifepool O53 Comprehensive coverage from low DNA input using novel NGS library preparation methods for WGS and WGBS C. Schumacher, S. Sandhu, T. Harkins, V. Makarov O54 Methods for large scale construction of robust PCR-free libraries for sequencing on Illumina HiSeqX platform H. DoddapaneniR. Glenn, Z. Momin, B. Dilrukshi, H. Chao, Q. Meng, B. Gudenkauf, R. Kshitij, J. Jayaseelan, C. Nessner, S. Lee, K. Blankenberg, L. Lewis, J. Hu, Y. Han, H. Dinh, S. Jireh, K. Walker, E. Boerwinkle, D. Muzny, R. Gibbs O55 Rapid capture methods for clinical sequencing J. Hu, K. Walker, C. Buhay, X. Liu, Q. Wang, R. Sanghvi, H. Doddapaneni, Y. Ding, N. Veeraraghavan, Y. Yang, E. Boerwinkle, A. L. Beaudet, C. M. Eng, D. M. Muzny, R. A. Gibbs O56 A diploid personal human genome model for better genomes from diverse sequence data K. C. C. Worley, Y. Liu, D. S. T. Hughes, S. C. Murali, R. A. Harris, A. C. English, X. Qin, O. A. Hampton, P. Larsen, C. Beck, Y. Han, M. Wang, H. Doddapaneni, C. L. Kovar, W. J. Salerno, A. Yoder, S. Richards, J. Rogers, J. R. Lupski, D. M. Muzny, R. A. Gibbs O57 Development of PacBio long range capture for detection of pathogenic structural variants Q. Meng, M. Bainbridge, M. Wang, H. Doddapaneni, Y. Han, D. Muzny, R. Gibbs O58 Rhesus macaques exhibit more non-synonymous variation but greater impact of purifying selection than humans R. A. Harris, M. Raveenedran, C. Xue, M. Dahdouli, L. Cox, G. Fan, B. Ferguson, J. Hovarth, Z. Johnson, S. Kanthaswamy, M. Kubisch, M. Platt, D. Smith, E. Vallender, R. Wiseman, X. Liu, J. Below, D. Muzny, R. Gibbs, F. Yu, J. Rogers O59 Assessing RNA structure disruption induced by single-nucleotide variation J. Lin, Y. Zhang, Z. Ouyang P1 A meta-analysis of genome-wide association studies of mitochondrial dna copy number A. Moore, Z. Wang, J. Hofmann, M. Purdue, R. Stolzenberg-Solomon, S. Weinstein, D. Albanes, C.-S. Liu, W.-L. Cheng, T.-T. Lin, Q. Lan, N. Rothman, S. Berndt P2 Missense polymorphic genetic combinations underlying down syndrome susceptibility E. S. Chen P4 The evaluation of alteration of ELAM-1 expression in the endometriosis patients H. Bahrami, A. Khoshzaban, S. Heidari Keshal P5 Obesity and the incidence of apolipoprotein E polymorphisms in an assorted population from Saudi Arabia population K. K. R. Alharbi P6 Genome-associated personalized antithrombotical therapy for patients with high risk of thrombosis and bleeding M. Zhalbinova, A. Akilzhanova, S. Rakhimova, M. Bekbosynova, S. Myrzakhmetova P7 Frequency of Xmn1 polymorphism among sickle cell carrier cases in UAE population M. Matar P8 Differentiating inflammatory bowel diseases by using genomic data: dimension of the problem and network organization N. Mili, R. Molinari, Y. Ma, S. Guerrier P9 Vulnerability of genetic variants to the risk of autism among Saudi children N. Elhawary, M. Tayeb, N. Bogari, N. Qotb P10 Chromatin profiles from ex vivo purified dopaminergic neurons establish a promising model to support studies of neurological function and dysfunction S. A. McClymont, P. W. Hook, L. A. Goff, A. McCallion P11 Utilization of a sensitized chemical mutagenesis screen to identify genetic modifiers of retinal dysplasia in homozygous Nr2e3rd7mice Y. Kong, J. R. Charette, W. L. Hicks, J. K. Naggert, L. Zhao, P. M. Nishina P12 Ion torrent next generation sequencing of recessive polycystic kidney disease in Saudi patients B. M. Edrees, M. Athar, F. A. Al-Allaf, M. M. Taher, W. Khan, A. Bouazzaoui, N. A. Harbi, R. Safar, H. Al-Edressi, A. Anazi, N. Altayeb, M. A. Ahmed, K. Alansary, Z. Abduljaleel P13 Digital expression profiling of Purkinje neurons and dendrites in different subcellular compartments A. Kratz, P. Beguin, S. Poulain, M. Kaneko, C. Takahiko, A. Matsunaga, S. Kato, A. M. Suzuki, N. Bertin, T. Lassmann, R. Vigot, P. Carninci, C. Plessy, T. Launey P14 The evolution of imperfection and imperfection of evolution: the functional and functionless fractions of the human genome D. Graur P16 Species-independent identification of known and novel recurrent genomic entities in multiple cancer patients J. Friis-Nielsen, J. M. Izarzugaza, S. Brunak P18 Discovery of active gene modules which are densely conserved across multiple cancer types reveal their prognostic power and mutually exclusive mutation patterns B. S. Soibam P19 Whole exome sequencing of dysplastic leukoplakia tissue indicates sequential accumulation of somatic mutations from oral precancer to cancer D. Das, N. Biswas, S. Das, S. Sarkar, A. Maitra, C. Panda, P. Majumder P21 Epigenetic mechanisms of carcinogensis by hereditary breast cancer genes J. J. Gruber, N. Jaeger, M. Snyder P22 RNA direct: a novel RNA enrichment strategy applied to transcripts associated with solid tumors K. Patel, S. Bowman, T. Davis, D. Kraushaar, A. Emerman, S. Russello, N. Henig, C. Hendrickson P23 RNA sequencing identifies gene mutations for neuroblastoma K. Zhang P24 Participation of SFRP1 in the modulation of TMPRSS2-ERG fusion gene in prostate cancer cell lines M. Rodriguez-Dorantes, C. D. Cruz-Hernandez, C. D. P. Garcia-Tobilla, S. Solorzano-Rosales P25 Targeted Methylation Sequencing of Prostate Cancer N. Jäger, J. Chen, R. Haile, M. Hitchins, J. D. Brooks, M. Snyder P26 Mutant TPMT alleles in children with acute lymphoblastic leukemia from México City and Yucatán, Mexico S. Jiménez-Morales, M. Ramírez, J. Nuñez, V. Bekker, Y. Leal, E. Jiménez, A. Medina, A. Hidalgo, J. Mejía P28 Genetic modifiers of Alström syndrome J. Naggert, G. B. Collin, K. DeMauro, R. Hanusek, P. M. Nishina P31 Association of genomic variants with the occurrence of angiotensin-converting-enzyme inhibitor (ACEI)-induced coughing among Filipinos E. M. Cutiongco De La Paz, R. Sy, J. Nevado, P. Reganit, L. Santos, J. D. Magno, F. E. Punzalan , D. Ona , E. Llanes, R. L. Santos-Cortes , R. Tiongco, J. Aherrera, L. Abrahan, P. Pagauitan-Alan; Philippine Cardiogenomics Study Group P32 The use of “humanized” mouse models to validate disease association of a de novo GARS variant and to test a novel gene therapy strategy for Charcot-Marie-Tooth disease type 2D K. H. Morelli, J. S. Domire, N. Pyne, S. Harper, R. Burgess P34 Molecular regulation of chondrogenic human induced pluripotent stem cells M. A. Gari, A. Dallol, H. Alsehli, A. Gari, M. Gari, A. Abuzenadah P35 Molecular profiling of hematologic malignancies: implementation of a variant assessment algorithm for next generation sequencing data analysis and clinical reporting M. Thomas, M. Sukhai, S. Garg, M. Misyura, T. Zhang, A. Schuh, T. Stockley, S. Kamel-Reid P36 Accessing genomic evidence for clinical variants at NCBI S. Sherry, C. Xiao, D. Slotta, K. Rodarmer, M. Feolo, M. Kimelman, G. Godynskiy, C. O’Sullivan, E. Yaschenko P37 NGS-SWIFT: a cloud-based variant analysis framework using control-accessed sequencing data from DBGAP/SRA C. Xiao, E. Yaschenko, S. Sherry P38 Computational assessment of drug induced hepatotoxicity through gene expression profiling C. Rangel-Escareño, H. Rueda-Zarate P40 Flowr: robust and efficient pipelines using a simple language-agnostic approach;ultraseq; fast modular pipeline for somatic variation calling using flowr S. Seth, S. Amin, X. Song, X. Mao, H. Sun, R. G. Verhaak, A. Futreal, J. Zhang P41 Applying “Big data” technologies to the rapid analysis of heterogenous large cohort data S. J. Whiite, T. Chiang, A. English, J. Farek, Z. Kahn, W. Salerno, N. Veeraraghavan, E. Boerwinkle, R. Gibbs P42 FANTOM5 web resource for the large-scale genome-wide transcription start site activity profiles of wide-range of mammalian cells T. Kasukawa, M. Lizio, J. Harshbarger, S. Hisashi, J. Severin, A. Imad, S. Sahin, T. C. Freeman, K. Baillie, A. Sandelin, P. Carninci, A. R. R. Forrest, H. Kawaji, The FANTOM Consortium P43 Rapid and scalable typing of structural variants for disease cohorts W. Salerno, A. English, S. N. Shekar, A. Mangubat, J. Bruestle, E. Boerwinkle, R. A. Gibbs P44 Polymorphism of glutathione S-transferases and sulphotransferases genes in an Arab population A. H. Salem, M. Ali, A. Ibrahim, M. Ibrahim P46 Genetic divergence of CYP3A5*3 pharmacogenomic marker for native and admixed Mexican populations J. C. Fernandez-Lopez, V. Bonifaz-Peña, C. Rangel-Escareño, A. Hidalgo-Miranda, A. V. Contreras P47 Whole exome sequence meta-analysis of 13 white blood cell, red blood cell, and platelet traits L. Polfus, CHARGE and NHLBI Exome Sequence Project Working Groups P48 Association of adipoq gene with type 2 diabetes and related phenotypes in african american men and women: The jackson heart study S. Davis, R. Xu, S. Gebeab, P Riestra, A Gaye, R. Khan, J. Wilson, A. Bidulescu P49 Common variants in casr gene are associated with serum calcium levels in koreans S. H. Jung, N. Vinayagamoorthy, S. H. Yim, Y. J. Chung P50 Inference of multiple-wave population admixture by modeling decay of linkage disequilibrium with multiple exponential functions Y. Zhou, S. Xu P51 A Bayesian framework for generalized linear mixed models in genome-wide association studies X. Wang, V. Philip, G. Carter P52 Targeted sequencing approach for the identification of the genetic causes of hereditary hearing impairment A. A. Abuzenadah, M. Gari, R. Turki, A. Dallol P53 Identification of enhancer sequences by ATAC-seq open chromatin profiling A. Uyar, A. Kaygun, S. Zaman, E. Marquez, J. George, D. Ucar P54 Direct enrichment for the rapid preparation of targeted NGS libraries C. L. Hendrickson, A. Emerman, D. Kraushaar, S. Bowman, N. Henig, T. Davis, S. Russello, K. Patel P56 Performance of the Agilent D5000 and High Sensitivity D5000 ScreenTape assays for the Agilent 4200 Tapestation System R. Nitsche, L. Prieto-Lafuente P57 ClinVar: a multi-source archive for variant interpretation M. Landrum, J. Lee, W. Rubinstein, D. Maglott P59 Association of functional variants and protein physical interactions of human MUTY homolog linked with familial adenomatous polyposis and colorectal cancer syndrome Z. Abduljaleel, W. Khan, F. A. Al-Allaf, M. Athar , M. M. Taher, N. Shahzad P60 Modification of the microbiom constitution in the gut using chicken IgY antibodies resulted in a reduction of acute graft-versus-host disease after experimental bone marrow transplantation A. Bouazzaoui, E. Huber, A. Dan, F. A. Al-Allaf, W. Herr, G. Sprotte, J. Köstler, A. Hiergeist, A. Gessner, R. Andreesen, E. Holler P61 Compound heterozygous mutation in the LDLRgene in Saudi patients suffering severe hypercholesterolemia F. Al-Allaf, A. Alashwal, Z. Abduljaleel, M. Taher, A. Bouazzaoui, H. Abalkhail, A. Al-Allaf, R. Bamardadh, M. Athar

Published
2016
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41. Prenatal exclusion of choroideremia

Author

van den Hurk, J. A. J. M., primary, van Zandvoort, P. M., additional, Brunsmann, F., additional, Pawlowitzki, I. H., additional, Holzgreve, W., additional, Szabo, P., additional, Cremers, F. P. M., additional, and van Oost, B. A., additional

Published
1992
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45. Design of a computer-controlled multileaf collimator for advanced electron radiotherapy

Author

Gauer, T, Albers, D, Cremers, F, Harmansa, R, Pellegrini, R, and Schmidt, R

Abstract

A multileaf collimator for electrons (eMLC) has been designed that fulfils the technical requirements for providing advanced irradiation techniques with electrons. In the present work, the basic design parameters of leaf material, leaf height, leaf width and number of leaves as well as leaf overtravel and leaf shape were determined such that an eMLC with motorized leaves can be manufactured by a company specialized in MLC technology. For this purpose, a manually driven eMLC with variable source-to-collimator distance (SCD) was used to evaluate the chosen leaf specification and investigate the impact of the SCD on the off-axis dose distribution. In order to select the final SCD of the eMLC, a compromise had to be found between maximum field size, minimum beam penumbra and necessary distance between eMLC and isocentre to eliminate patient realignments during gantry rotation. As a result, the eMLC is placed according to the target position at 72 and 84 cm SCD, respectively. This feature will be achieved by interchangeable distance holders. At these SCDs, the corresponding maximum field sizes at 100 cm source-to-isocentre distance are 20 × 20 cm and 17 × 17 cm, respectively. Finally, the off-axis dose distribution at the maximum opening of the eMLC was improved by fine-tuning the settings of the accelerator jaws and introducing trimmer bars above the eMLC. Following this optimization, a prototype eMLC consisting of 2 × 24 computer-controlled brass leaves is manufactured by 3D Line Medical Systems.

Published
2006

47. Monte Carlo simulation of a prototype photodetector used in radiotherapy

Author

Kausch, C, Cremers, F, Albers, D, Schmidt, R, and Schreiber, B

Abstract

The imaging performance of prototype electronic portal imaging devices (EPID) has been investigated. Monte Carlo simulations have been applied to calculate the modulation transfer function (MTF(f)), the noise power spectrum (NPS(f)) and the detective quantum efficiency (DQE(f)) for different new type of EPIDs, which consist of a detector combination of metal or polyethylene (PE), a phosphor layer of Gd2O2S and a flat array of photodiodes. The simulated results agree well with measurements. Based on simulated results, possible optimization of these devices is discussed.

Published
2000
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48. Familial idiopathic premature ovarian failure: an overrated and underestimated genetic disease?

Author

van Kasteren, Y M, Hundscheid, R D, Smits, A P, Cremers, F P, van Zonneveld, P, and Braat, D D

Abstract

The incidence of familial cases of premature ovarian failure varies from 4 to 31%. Recall bias may explain part of the variance. Thorough evaluation of alleged affected relatives showed a lower incidence than the original family history suggested. In the present study the incidence of familial cases was 12.7%. Pedigree studies on affected families showed a mode of inheritance suggestive of autosomal dominant sex-limited transmission or X-linked inheritance with incomplete penetrance. An adequate family history can distinguish between familial or sporadic premature ovarian failure. The risk of female relatives developing premature ovarian failure may be as high as 100% in familial premature ovarian failure, or as low as 1% in sporadic cases.

Published
1999
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49. KearnsSayre syndrome with a phenocopy of choroideremia instead of pigmentary retinopathy

Author

Herzberg, N. H., Schooneveld, M. J. van, Bleeker-Wagemakers, E. M., Zwart, R., Cremers, F. P.M., Knaap, M. S. van der, Bolhuis, P. A., and de Visser, M.

Abstract

Mitochondrial DNA (mtDNA) was deleted in a patient with Kearns-Sayre syndrome (KSS) presenting with a choroideremia-like fundus picture instead of pigmentary retinopathy. No evidence for X-linked choroideremia was present, and because of the strong association between KSS and deleted mtDNA, we suggest that choroideremia is a phenocopy and can be part of KSS.

Published
1993

50. Epidermal growth factor induces rapid and transient association of phospholipase C-gamma 1 with EGF-receptor and filamentous actin at membrane ruffles of A431 cells.

Author

Diakonova, M, Payrastre, B, van Velzen, A G, Hage, W J, van Bergen en Henegouwen, P M, Boonstra, J, Cremers, F F, and Humbel, B M

Abstract

Addition of epidermal growth factor to A431 cells results in dramatic changes in cell morphology. Initially the cells form membrane ruffles accompanied by increased actin polymerization, followed by cell rounding. Activation of the tyrosine kinase of the receptor by binding epidermal growth factor leads also to phosphorylation and activation of phospholipase C-gamma 1, a key enzyme in the phosphoinositide pathway. In this study we have investigated the localization of phospholipase C-gamma 1 during cell activation by epidermal growth factor. It is shown that addition of the growth factor to A431 cells leads to a translocation of phospholipase C-gamma 1 from the cytosol to the membrane fraction. Interestingly, this relocation is exclusively directed to the membrane ruffles. Most of the phospholipase C-gamma 1 associates to the membrane and a small fraction to the underlying skeleton. Immunocytochemical studies demonstrated that phospholipase C-gamma 1 co-localizes with the epidermal growth factor receptor and also filamentous actin at the membrane ruffles. Moreover, using anti-phosphotyrosine antibodies we found that the membrane ruffles are significantly enriched in phosphotyrosyl proteins. Between 5 and 10 minutes after stimulation the membrane ruffles disappear and also the co-localization of phospholipase C-gamma 1 with the epidermal growth factor receptor and filamentous actin. These results support the notion that activation of A431 cells by epidermal growth factor leads to the formation of a signalling complex of its receptor, phospholipase C-gamma 1 and filamentous actin which is primarily localized at membrane ruffles.

Published
1995

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