36 results on '"Rupps, R."'
Search Results
2. Phenotypic and molecular characterization of a novel DCX deletion and a review of the literature
- Author
-
Chou, A, Boerkoel, C, du Souich, C, and Rupps, R
- Published
- 2009
- Full Text
- View/download PDF
3. Recurrent trisomy 21: four cases in three generations
- Author
-
Gair, J L, Arbour, L, Rupps, R, Jiang, R, Bruyère, H, and Robinson, W P
- Published
- 2005
4. Phenotypic spectrum associated with PTCHD1 deletions and truncating mutations includes intellectual disability and autism spectrum disorder
- Author
-
Chaudhry, A., Noor, A., Degagne, B., Baker, K., Bok, L. A., Brady, A. F., Chitayat, D., Chung, B. H., Cytrynbaum, C., Dyment, D., Filges, I., Helm, B., Hutchison, H. T., Jeng, L. J. B., Laumonnier, F., Marshall, C. R., Menzel, M., Parkash, S., Parker, M. J., Raymond, L. F., Rideout, A. L., Roberts, W., Rupps, R., Schanze, I., Schrander-Stumpel, C. T. R. M., Speevak, M. D., Stavropoulos, D. J., Stevens, S. J. C., Thomas, E. R. A., Toutain, A., Vergano, S., Weksberg, R., Scherer, S. W., Vincent, J. B., Carter, M. T., RS: GROW - Developmental Biology, RS: GROW - R4 - Reproductive and Perinatal Medicine, Afdeling Onderwijs FHML, and MUMC+: DA Pat Cytologie (9)
- Subjects
X-linked ,Adult ,Male ,Adolescent ,Autism Spectrum Disorder ,PTCHD1 ,Facies ,Infant ,Membrane Proteins ,Exons ,Young Adult ,Phenotype ,Child, Preschool ,Intellectual Disability ,Mutation ,Humans ,Female ,Child ,Sequence Deletion - Abstract
Studies of genomic copy number variants (CNVs) have identified genes associated with autism spectrum disorder (ASD) and intellectual disability (ID) such as NRXN1, SHANK2, SHANK3 and PTCHD1. Deletions have been reported in PTCHD1 however there has been little information available regarding the clinical presentation of these individuals. Herein we present 23 individuals with PTCHD1 deletions or truncating mutations with detailed phenotypic descriptions. The results suggest that individuals with disruption of the PTCHD1 coding region may have subtle dysmorphic features including a long face, prominent forehead, puffy eyelids and a thin upper lip. They do not have a consistent pattern of associated congenital anomalies or growth abnormalities. They have mild to moderate global developmental delay, variable degrees of ID, and many have prominent behavioral issues. Over 40% of subjects have ASD or ASD-like behaviors. The only consistent neurological findings in our cohort are orofacial hypotonia and mild motor incoordination. Our findings suggest that hemizygous PTCHD1 loss of function causes an X-linked neurodevelopmental disorder with a strong propensity to autistic behaviors. Detailed neuropsychological studies are required to better define the cognitive and behavioral phenotype.
- Published
- 2014
5. Two Sisters with Congenital Blindness caused by Osteoporosis-pseudoglioma Syndrome due to new Mutations in the LPR5 Gene
- Author
-
Welinder, L., primary, Robitaille, J.M., additional, Boerkoel, C.F., additional, Rupps, R., additional, and Lyons, C., additional
- Published
- 2015
- Full Text
- View/download PDF
6. Phenotypic and molecular characterization of a novelDCXdeletion and a review of the literature
- Author
-
Chou, A, primary, Boerkoel, C, additional, du Souich, C, additional, and Rupps, R, additional
- Published
- 2009
- Full Text
- View/download PDF
7. Cloning, sequencing, and viscometric adhesion analysis of heat-resistant agglutinin 1, an integral membrane hemagglutinin from Escherichia coli O9:H10:K99
- Author
-
Lutwyche, P, primary, Rupps, R, additional, Cavanagh, J, additional, Warren, R A, additional, and Brooks, D E, additional
- Published
- 1994
- Full Text
- View/download PDF
8. Genome-wide sequencing and the clinical diagnosis of genetic disease: The CAUSES study.
- Author
-
Elliott AM, Adam S, du Souich C, Lehman A, Nelson TN, van Karnebeek C, Alderman E, Armstrong L, Aubertin G, Blood K, Boelman C, Boerkoel C, Bretherick K, Brown L, Chijiwa C, Clarke L, Couse M, Creighton S, Watts-Dickens A, Gibson WT, Gill H, Tarailo-Graovac M, Hamilton S, Heran H, Horvath G, Huang L, Hulait GK, Koehn D, Lee HK, Lewis S, Lopez E, Louie K, Niederhoffer K, Matthews A, Meagher K, Peng JJ, Patel MS, Race S, Richmond P, Rupps R, Salvarinova R, Seath K, Selby K, Steinraths M, Stockler S, Tang K, Tyson C, van Allen M, Wasserman W, Mwenifumbo J, and Friedman JM
- Abstract
Genome-wide sequencing (GWS) is a standard of care for diagnosis of suspected genetic disorders, but the proportion of patients found to have pathogenic or likely pathogenic variants ranges from less than 30% to more than 60% in reported studies. It has been suggested that the diagnostic rate can be improved by interpreting genomic variants in the context of each affected individual's full clinical picture and by regular follow-up and reinterpretation of GWS laboratory results. Trio exome sequencing was performed in 415 families and trio genome sequencing in 85 families in the CAUSES study. The variants observed were interpreted by a multidisciplinary team including laboratory geneticists, bioinformaticians, clinical geneticists, genetic counselors, pediatric subspecialists, and the referring physician, and independently by a clinical laboratory using standard American College of Medical Genetics and Genomics (ACMG) criteria. Individuals were followed for an average of 5.1 years after testing, with clinical reassessment and reinterpretation of the GWS results as necessary. The multidisciplinary team established a diagnosis of genetic disease in 43.0% of the families at the time of initial GWS interpretation, and longitudinal follow-up and reinterpretation of GWS results produced new diagnoses in 17.2% of families whose initial GWS interpretation was uninformative or uncertain. Reinterpretation also resulted in rescinding a diagnosis in four families (1.9%). Of the families studied, 33.6% had ACMG pathogenic or likely pathogenic variants related to the clinical indication. Close collaboration among clinical geneticists, genetic counselors, laboratory geneticists, bioinformaticians, and individuals' primary physicians, with ongoing follow-up, reanalysis, and reinterpretation over time, can improve the clinical value of GWS., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)
- Published
- 2022
- Full Text
- View/download PDF
9. An approach to rapid characterization of DMD copy number variants for prenatal risk assessment.
- Author
-
Chin HL, O'Neill K, Louie K, Brown L, Schlade-Bartusiak K, Eydoux P, Rupps R, Farahani A, Boerkoel CF, and Jones SJM
- Subjects
- Adult, Chromosome Breakpoints, Chromosome Duplication, Chromosomes, Human, X, Comparative Genomic Hybridization, Exons, Female, Genetic Association Studies methods, Genetic Predisposition to Disease, Humans, Male, Pedigree, Pregnancy, Sequence Analysis, DNA, DNA Copy Number Variations, Dystrophin genetics, Genetic Testing methods, Muscular Dystrophy, Duchenne diagnosis, Muscular Dystrophy, Duchenne genetics, Prenatal Diagnosis methods
- Abstract
Prenatal detection of structural variants of uncertain significance, including copy number variants (CNV), challenges genetic counseling, and creates ambiguity for expectant parents. In Duchenne muscular dystrophy, variant classification and phenotypic severity of CNVs are currently assessed by familial segregation, prediction of the effect on the reading frame, and precedent data. Delineation of pathogenicity by familial segregation is limited by time and suitable family members, whereas analytical tools can rapidly delineate potential consequences of variants. We identified a duplication of uncertain significance encompassing a portion of the dystrophin gene (DMD) in an unaffected mother and her male fetus. Using long-read whole genome sequencing and alignment of short reads, we rapidly defined the precise breakpoints of this variant in DMD and could provide timely counseling. The benign nature of the variant was substantiated, more slowly, by familial segregation to a healthy maternal uncle. We find long-read whole genome sequencing of clinical utility in a prenatal setting for accurate and rapid characterization of structural variants, specifically a duplication involving DMD., (© 2021 Wiley Periodicals LLC.)
- Published
- 2021
- Full Text
- View/download PDF
10. Prenatal Autoimmune Disease, Multisystem, Infantile Onset-like Phenotype and Proximal Renal Tubular Dysplasia Associated With STAT3 Mutation.
- Author
-
Terry J, Langlois S, Rupps R, and Gill H
- Subjects
- Adult, Autoimmune Diseases diagnosis, Autoimmune Diseases embryology, Autoimmune Diseases genetics, Female, Fetal Death, Genetic Markers, Heterozygote, Humans, Kidney Tubules, Proximal embryology, Mutation, Phenotype, Pregnancy, Autoimmune Diseases pathology, Kidney Tubules, Proximal abnormalities, Prenatal Diagnosis, STAT3 Transcription Factor genetics
- Abstract
Activating heterozygous germline mutations in the signal transducer and activator of transcription 3 ( STAT3 ) gene are associated with the rare autoimmune disorder autoimmune disease, multisystem, infantile onset (ADMIO). The phenotype of ADMIO is typified by hypogammaglobulinemia and onset of autoimmune phenomena during early childhood that include diabetes and autoimmune enteritis. This case report describes in utero onset of precocious lymphocyte maturation, autoimmune enteropathy-like inflammation, and proximal renal tubular dysplasia associated with a novel de novo heterozygous STAT3 mutation. The findings expand the phenotype associated with activating STAT3 mutations and suggest that the impact of the immunological abnormalities associated with ADMIO can begin prior to birth.
- Published
- 2020
- Full Text
- View/download PDF
11. Familial impairment of vocal cord mobility in childhood with clubfoot.
- Author
-
Shaw R, Dias C, Ludemann J, Rupps R, Tsai V, and Lehman A
- Subjects
- Adult, Child, Child, Preschool, Clubfoot etiology, Clubfoot genetics, Craniofacial Abnormalities genetics, Family, Female, Humans, Male, Pedigree, Phenotype, Vocal Cord Paralysis genetics, Vocal Cords physiopathology, Vocal Cord Paralysis physiopathology
- Abstract
We report on a family with three siblings, male and female, affected by congenital bilateral limitation of vocal cord abduction, with the additional finding of clubfeet in two. The paternal family history suggests an autosomal dominant inheritance. The siblings and father also have mild craniofacial features, which may be an expression of variability or may be unrelated. The association between congenital vocal cord paralysis and clubfeet has been reported with additional major features or in the context of Charcot-Marie-Tooth disease. However, the two in isolation have only been reported in one other family previously. Genomic analyses of the family, including chromosomal microarray and exome sequencing, showed neither a likely pathogenic variant in a known disease gene nor a compelling candidate gene variant. We propose that the association of these two findings constitutes a novel recognizable phenotype, for which a genetic cause remains undetermined.
- Published
- 2018
- Full Text
- View/download PDF
12. Chitayat-Hall and Schaaf-Yang syndromes:a common aetiology: expanding the phenotype of MAGEL2 -related disorders.
- Author
-
Jobling R, Stavropoulos DJ, Marshall CR, Cytrynbaum C, Axford MM, Londero V, Moalem S, Orr J, Rossignol F, Lopes FD, Gauthier J, Alos N, Rupps R, McKinnon M, Adam S, Nowaczyk MJM, Walker S, Scherer SW, Nassif C, Hamdan FF, Deal CL, Soucy JF, Weksberg R, Macleod P, Michaud JL, and Chitayat D
- Subjects
- Adolescent, Adult, Arthrogryposis physiopathology, Child, Exome genetics, Female, Growth Hormone deficiency, Humans, Intellectual Disability physiopathology, Male, Pedigree, Phenotype, Exome Sequencing, Young Adult, Arthrogryposis genetics, Growth Hormone genetics, Intellectual Disability genetics, Proteins genetics
- Abstract
Background: Chitayat-Hall syndrome, initially described in 1990, is a rare condition characterised by distal arthrogryposis, intellectual disability, dysmorphic features and hypopituitarism, in particular growth hormone deficiency. The genetic aetiology has not been identified., Methods and Results: We identified three unrelated families with a total of six affected patients with the clinical manifestations of Chitayat-Hall syndrome. Through whole exome or whole genome sequencing, pathogenic variants in the MAGEL2 gene were identified in all affected patients. All disease-causing sequence variants detected are predicted to result in a truncated protein, including one complex variant that comprised a deletion and inversion., Conclusions: Chitayat-Hall syndrome is caused by pathogenic variants in MAGEL2 and shares a common aetiology with the recently described Schaaf-Yang syndrome. The phenotype of MAGEL2 -related disorders is expanded to include growth hormone deficiency as an important and treatable complication., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
- Published
- 2018
- Full Text
- View/download PDF
13. FOXP1 haploinsufficiency: Phenotypes beyond behavior and intellectual disability?
- Author
-
Myers A, du Souich C, Yang CL, Borovik L, Mwenifumbo J, Rupps R, Study C, Lehman A, and Boerkoel CF
- Subjects
- Amino Acid Sequence, Autism Spectrum Disorder diagnostic imaging, Female, Haploinsufficiency, Humans, Infant, Newborn, Intellectual Disability diagnostic imaging, Language Disorders diagnostic imaging, Lung diagnostic imaging, Lung Diseases diagnosis, Male, Models, Molecular, Mutation, Phenotype, Protein Domains, Sequence Alignment, Exome Sequencing, Autism Spectrum Disorder genetics, Forkhead Transcription Factors genetics, Intellectual Disability genetics, Language Disorders genetics, Lung Diseases genetics, Repressor Proteins genetics
- Abstract
The forkhead box (FOX) transcription factors have roles in development, carcinogenesis, metabolism, and immunity. In humans FOXP1 mutations have been associated with language and speech defects, intellectual disability, autism spectrum disorder, facial dysmorphisms, and congenital anomalies of the kidney and urinary tract. In mice, Foxp1 plays critical roles in development of the spinal motor neurons, lymphocytes, cardiomyocytes, foregut, and skeleton. We hypothesized therefore that mutations of FOXP1 affect additional tissues in some humans. Supporting this hypothesis, we describe two individuals with novel variants of FOXP1 (NM_032682.5:c.975-2A>C and NM_032682.5:c.1574G>A) and additional features. One had a lung disease resembling neuroendocrine cell hyperplasia of infancy (NEHI), and the second had a skeletal disorder with undertubulation of the long bones and relapsing-remitting fevers associated with flushing and edema. Although attribution of these traits to mutation of FOXP1 requires ascertainment of additional patients, we hypothesize that the variable expression of these additional features might arise by means of stochastic developmental variation., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2017
- Full Text
- View/download PDF
14. Phenotypic evolution of UNC80 loss of function.
- Author
-
Valkanas E, Schaffer K, Dunham C, Maduro V, du Souich C, Rupps R, Adams DR, Baradaran-Heravi A, Flynn E, Malicdan MC, Gahl WA, Toro C, and Boerkoel CF
- Subjects
- Child, Child, Preschool, Developmental Disabilities complications, Developmental Disabilities physiopathology, Exome genetics, Failure to Thrive complications, Failure to Thrive physiopathology, Female, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, Paraplegia complications, Paraplegia physiopathology, RNA Stability genetics, Siblings, Carrier Proteins genetics, Developmental Disabilities genetics, Failure to Thrive genetics, Membrane Proteins genetics, Paraplegia genetics
- Abstract
Failure to thrive arises as a complication of a heterogeneous group of disorders. We describe two female siblings with spastic paraplegia and global developmental delay but also, atypically for the HSPs, poor weight gain classified as failure to thrive. After extensive clinical and biochemical investigations failed to identify the etiology, we used exome sequencing to identify biallelic UNC80 mutations (NM_032504.1:c.[3983-3_3994delinsA];[2431C>T]. The paternally inherited NM_032504.1:c.3983-3_3994delinsA is predicted to encode p.Ser1328Argfs*19 and the maternally inherited NM_032504.1:c.2431C>T is predicted to encode p.Arg811*. No UNC80 mRNA was detectable in patient cultured skin fibroblasts, suggesting UNC80 loss of function by nonsense mediated mRNA decay. Further supporting the UNC80 mutations as causative of these siblings' disorder, biallelic mutations in UNC80 have recently been described among individuals with an overlapping phenotype. This report expands the disease spectrum associated with UNC80 mutations. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2016
- Full Text
- View/download PDF
15. Phenotypic expansion of TBX4 mutations to include acinar dysplasia of the lungs.
- Author
-
Szafranski P, Coban-Akdemir ZH, Rupps R, Grazioli S, Wensley D, Jhangiani SN, Popek E, Lee AF, Lupski JR, Boerkoel CF, and Stankiewicz P
- Subjects
- Alleles, Autopsy, Chromosomes, Human, Pair 16, DNA Copy Number Variations, DNA Mutational Analysis, Fatal Outcome, Female, Genotype, Heterozygote, Humans, Infant, Newborn, Karyotype, Lung pathology, Pedigree, Radiography, Thoracic, Genetic Association Studies, Lung abnormalities, Mutation, Phenotype, T-Box Domain Proteins genetics
- Abstract
Mutations in the T-box transcription factor TBX4 gene have been reported in patients with Ischiocoxopodopatellar syndrome (MIM# 147891) and childhood-onset pulmonary arterial hypertension. Whole exome sequencing of DNA from a 1 day old deceased newborn, with severe diffuse developmental lung disorder exhibiting features of acinar dysplasia, and her unaffected parents identified a de novo TBX4 missense mutation p.E86Q (c.256G>C) in the DNA-binding T-box domain. We propose phenotypic expansion of the TBX4-related clinical disease spectrum to include acinar dysplasia of the lungs. The reported mutation is the first identified genetic variant causative for acinar dysplasia. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2016
- Full Text
- View/download PDF
16. Complex translocation disrupting TCF4 and altering TCF4 isoform expression segregates as mild autosomal dominant intellectual disability.
- Author
-
Maduro V, Pusey BN, Cherukuri PF, Atkins P, du Souich C, Rupps R, Limbos M, Adams DR, Bhatt SS, Eydoux P, Links AE, Lehman A, Malicdan MC, Mason CE, Morimoto M, Mullikin JC, Sear A, Van Karnebeek C, Stankiewicz P, Gahl WA, Toro C, and Boerkoel CF
- Subjects
- Alternative Splicing genetics, Child, Facies, Female, Humans, Hyperventilation genetics, Mutation genetics, Polymerase Chain Reaction, Polymorphism, Single Nucleotide genetics, Promoter Regions, Genetic genetics, Transcription Factor 4, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics, Intellectual Disability genetics, Protein Isoforms genetics, Transcription Factors genetics, Translocation, Genetic genetics
- Abstract
Background: Mutations of TCF4, which encodes a basic helix-loop-helix transcription factor, cause Pitt-Hopkins syndrome (PTHS) via multiple genetic mechanisms. TCF4 is a complex locus expressing multiple transcripts by alternative splicing and use of multiple promoters. To address the relationship between mutation of these transcripts and phenotype, we report a three-generation family segregating mild intellectual disability with a chromosomal translocation disrupting TCF4., Results: Using whole genome sequencing, we detected a complex unbalanced karyotype disrupting TCF4 (46,XY,del(14)(q23.3q23.3)del(18)(q21.2q21.2)del(18)(q21.2q21.2)inv(18)(q21.2q21.2)t(14;18)(q23.3;q21.2)(14pter®14q23.3::18q21.2®18q21.2::18q21.1®18qter;18pter®18q21.2::14q23.3®14qter). Subsequent transcriptome sequencing, qRT-PCR and nCounter analyses revealed that cultured skin fibroblasts and peripheral blood had normal expression of genes along chromosomes 14 or 18 and no marked changes in expression of genes other than TCF4. Affected individuals had 12-33 fold higher mRNA levels of TCF4 than did unaffected controls or individuals with PTHS. Although the derivative chromosome generated a PLEKHG3-TCF4 fusion transcript, the increased levels of TCF4 mRNA arose from transcript variants originating distal to the translocation breakpoint, not from the fusion transcript., Conclusions: Although validation in additional patients is required, our findings suggest that the dysmorphic features and severe intellectual disability characteristic of PTHS are partially rescued by overexpression of those short TCF4 transcripts encoding a nuclear localization signal, a transcription activation domain, and the basic helix-loop-helix domain.
- Published
- 2016
- Full Text
- View/download PDF
17. Congenital Bilateral Retinal Detachment in Two Siblings with Osteoporosis-Pseudoglioma Syndrome.
- Author
-
Welinder LG, Robitaille JM, Rupps R, Boerkoel CF, and Lyons CJ
- Subjects
- DNA Mutational Analysis, Female, Fractures, Compression diagnostic imaging, Heterozygote, Humans, Infant, Radiography, Retinal Detachment diagnostic imaging, Siblings, Ultrasonography, Low Density Lipoprotein Receptor-Related Protein-5 genetics, Mutation, Osteogenesis Imperfecta genetics, Retinal Detachment congenital
- Abstract
The birth of a bilaterally blind child is catastrophic for families and a challenging diagnostic and management problem for ophthalmologists. Early identification of the underlying cause and its genetic basis helps initiate possible treatment, delineate prognosis, and identify risks for future pregnancies. In some cases, an early diagnosis can also influence the treatment of other family members. We report two sisters with bilateral retinal detachment and retro-lental masses from birth with no detectable NDP or FZD4 mutations. They were born to parents without detectable retinal anomalies. At 1 year of age, the elder sister had low impact bone fractures, and further evaluation identified severe osteopenia and multiple spinal compression fractures. Molecular testing identified biallelic lipoprotein receptor-related protein 5 (LRP5) mutations (NM_002335.3:c. [889dupA]; [2827 + 1G > A]) confirming a diagnosis of osteoporosis-pseudoglioma (OPPG) syndrome. After this diagnosis, the father and mother were found to have low bone mass and the father started on therapy. We conclude that early detection of LRP5 mutations is important for initiation of treatment of reduced bone density in the patients and their carrier relatives.
- Published
- 2015
- Full Text
- View/download PDF
18. Desmosterolosis: an illustration of diagnostic ambiguity of cholesterol synthesis disorders.
- Author
-
Dias C, Rupps R, Millar B, Choi K, Marra M, Demos M, Kratz LE, and Boerkoel CF
- Subjects
- Abnormalities, Multiple metabolism, Abnormalities, Multiple pathology, Diagnosis, Differential, Female, Humans, Lipid Metabolism, Inborn Errors metabolism, Lipid Metabolism, Inborn Errors pathology, Abnormalities, Multiple diagnosis, Cholesterol biosynthesis, Lipid Metabolism, Inborn Errors diagnosis
- Abstract
Desmosterolosis is an autosomal recessive disorder of cholesterol biosynthesis caused by biallelic mutations of DHCR24 (homozygous or compound heterozygous), which encodes 3-β-hydroxysterol Δ-24-reductase. We report two sisters homozygous for the 571G>A (E191K) DHCR24 mutation. Comparison of the propositae to other reported individuals shows that psychomotor developmental delay, failure to thrive, dysgenesis of the corpus callosum, cerebral white matter atrophy and spasticity likely constitute the minimal desmosterolosis phenotype. The nonspecific features of desmosterolosis make it difficult to suspect clinically and therefore screening for it should be entertained early in the diagnostic evaluation.
- Published
- 2014
- Full Text
- View/download PDF
19. A cryptic familial rearrangement of 11p15.5, involving both imprinting centers, in a family with a history of short stature.
- Author
-
Brown LA, Rupps R, Peñaherrera MS, Robinson WP, Patel MS, Eydoux P, and Boerkoel CF
- Subjects
- Adolescent, Adult, Base Sequence, Child, Preschool, Chromosomes, Human, Pair 11, DNA Methylation, Facies, Family, Female, Gene Rearrangement genetics, Growth Disorders genetics, Humans, Male, Oligonucleotide Array Sequence Analysis, Gene Duplication genetics, Genomic Imprinting genetics, Silver-Russell Syndrome genetics
- Abstract
Silver-Russell syndrome (SRS) is a heterogeneous disorder characterized by intrauterine and postnatal growth retardation, dysmorphic facial features and body asymmetry. Both hypomethylation of the telomeric imprinting control region 1 (ICR1) at 11p15.5 and maternal duplication of 11p15.5 have been implicated in the etiology of this disorder. Here we report the origin and segregation of the first reported between-arm intrachromosomal insertion of 11p15.5 that encompasses both ICR1 and ICR2 in a multigenerational family with a history of short stature. One (or any odd number) crossover within the centromeric segment during meiosis would produce recombinant chromosomes; one with a duplication of the inserted segment and the other a deletion. In this 4-generation family, there were six instances of transmission of the recombinant chromosome with duplication of the11p15.5 segment, which leads to a SRS phenotype when maternally inherited and a Beckwith-Wiedemann phenotype when paternally transmitted. The size of the duplicated region is ~1.9 Mb as determined by microarray analysis. This study provides further evidence that maternally inherited duplications of 11p15.5 result in a SRS phenotype that includes short stature and other variable features. The methylation status of the extra copy of the duplicated region of 11p15.5 ultimately predicts the resulting phenotype. Thus, the different phenotype based on parental mode of transmission is of importance in the genetic counseling of these patients., (© 2014 Wiley Periodicals, Inc.)
- Published
- 2014
- Full Text
- View/download PDF
20. Novel Mutations in FA2H-Associated Neurodegeneration: An Underrecognized Condition?
- Author
-
Rupps R, Hukin J, Balicki M, Mercimek-Mahmutoglu S, Rolfs A, and Dias C
- Abstract
Hereditary spastic paraplegias and related genetically heterogeneous disorders may be difficult to distinguish clinically. The FA2H gene has been associated with autosomal recessive neurodegenerative phenotypes encompassing spastic paraplegia with or without dystonia, and demyelinating leukodystrophy. To date, few individuals with mutations in the FA2H gene have been described. We report a 5-year-old girl of mixed Filipino and Vietnamese origin who presented with progressive lower limb spasticity and periventricular leukomalacia. The clinical diagnosis of FA2H-associated neurodegeneration was confirmed on the basis of 2 novel mutations in compound heterozygosity in the FA2H gene (p.S70L/p.P323L). This family highlights that FA2H-associated disorders may be underrecognized in children with neurodegeneration of many different ethnicities. Magnetic resonance imaging features play an important role as diagnostic clues in this and other hereditary spastic paraplegias. The consideration of this diagnosis is essential in providing families with important information on prognosis, as well as accurate genetic counseling.
- Published
- 2013
- Full Text
- View/download PDF
21. Recurrent subacute post-viral onset of ataxia associated with a PRF1 mutation.
- Author
-
Dias C, McDonald A, Sincan M, Rupps R, Markello T, Salvarinova R, Santos RF, Menghrajani K, Ahaghotu C, Sutherland DP, Fortuno ES 3rd, Kollmann TR, Demos M, Friedman JM, Speert DP, Gahl WA, and Boerkoel CF
- Subjects
- Child, Child, Preschool, Exome genetics, Fatal Outcome, Female, Homozygote, Humans, Infant, Infant, Newborn, Inflammasomes metabolism, Interleukin-1beta biosynthesis, Magnetic Resonance Imaging, Male, Pedigree, Recurrence, Sequence Analysis, DNA, Ataxia genetics, Ataxia virology, Homeodomain Proteins genetics, Mutation genetics
- Abstract
Inflammation is an important contributor to pediatric and adult neurodegeneration. Understanding the genetic determinants of neuroinflammation provides valuable insight into disease mechanism. We characterize a disorder of recurrent immune-mediated neurodegeneration. We report two sisters who presented with neurodegeneration triggered by infections. The proband, a previously healthy girl, presented at 22.5 months with ataxia and dysarthria following mild gastroenteritis. MRI at onset showed a symmetric signal abnormality of the cerebellar and peritrigonal white matter. Following a progressive course of partial remissions and relapses, she died at 5 years of age. Her older sister had a similar course following varicella infection, she died within 13 months. Both sisters had unremarkable routine laboratory testing, with exception of a transient mild cytopenia in the proband 19 months after presentation. Exome sequencing identified a biallelic perforin1 mutation (PRF1; p.R225W) previously associated with familial hemophagocytic lymphohistiocytosis (FHL). In contrast to FHL, these girls did not have hematopathology or cytokine overproduction. However, 3 years after disease onset, the proband had markedly deficient interleukin-1 beta (IL-1β) production. These observations extend the spectrum of disease associated with perforin mutations to immune-mediated neurodegeneration triggered by infection and possibly due to primary immunodeficiency.
- Published
- 2013
- Full Text
- View/download PDF
22. Life-history chronicle for a patient with the recently described chromosome 4q21 microdeletion syndrome.
- Author
-
Tsang E, Rupps R, McGillivray B, Eydoux P, Marra M, Arbour L, Langlois S, Friedman JM, and Zahir FR
- Subjects
- Abnormalities, Multiple genetics, Abnormalities, Multiple pathology, Adult, Developmental Disabilities genetics, Developmental Disabilities pathology, Fatal Outcome, Female, Humans, Intellectual Disability genetics, Intellectual Disability pathology, Phenotype, Syndrome, Young Adult, Chromosome Deletion, Chromosome Disorders genetics, Chromosome Disorders pathology, Chromosomes, Human, Pair 4 genetics
- Abstract
[Bonnet et al. (2010); J Med Genet 47: 377-384] recently suggested a 4q21 microdeletion syndrome with several common features, including severe intellectual disability, lack of speech, hypotonia, significant growth restriction, and distinctive facial features. Overlap of the deleted regions of 13 patients, including a patient we previously reported, delineates a critical region, with PRKG2 and RASGEF1B emerging as candidate genes. Here we provide a detailed clinical report and photographic life history of our previously reported patient. Previous case reports of this new syndrome have not described the prognosis or natural history of these patients., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2012
- Full Text
- View/download PDF
23. Subtelomeric deletion of chromosome 10p15.3: clinical findings and molecular cytogenetic characterization.
- Author
-
DeScipio C, Conlin L, Rosenfeld J, Tepperberg J, Pasion R, Patel A, McDonald MT, Aradhya S, Ho D, Goldstein J, McGuire M, Mulchandani S, Medne L, Rupps R, Serrano AH, Thorland EC, Tsai AC, Hilhorst-Hofstee Y, Ruivenkamp CA, Van Esch H, Addor MC, Martinet D, Mason TB, Clark D, Spinner NB, and Krantz ID
- Subjects
- Child, Female, Humans, Infant, Infant, Newborn, Male, Chromosome Deletion, Chromosomes, Human, Pair 10, Telomere
- Abstract
We describe 19 unrelated individuals with submicroscopic deletions involving 10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our knowledge, only two individuals with isolated, submicroscopic 10p15.3 deletion have been reported to date; however, only limited clinical information is available for these probands and the deleted region has not been molecularly mapped. Comprehensive clinical history was obtained for 12 of the 19 individuals described in this study. Common features among these 12 individuals include: cognitive/behavioral/developmental differences (11/11), speech delay/language disorder (10/10), motor delay (10/10), craniofacial dysmorphism (9/12), hypotonia (7/11), brain anomalies (4/6) and seizures (3/7). Parental studies were performed for nine of the 19 individuals; the 10p15.3 deletion was de novo in seven of the probands, not maternally inherited in one proband and inherited from an apparently affected mother in one proband. Molecular mapping of the 19 individuals reported in this study has identified two genes, ZMYND11 (OMIM 608668) and DIP2C (OMIM 611380; UCSC Genome Browser), mapping within 10p15.3 which are most commonly deleted. Although no single gene has been identified which is deleted in all 19 individuals studied, the deleted region in all but one individual includes ZMYND11 and the deleted region in all but one other individual includes DIP2C. There is not a clearly identifiable phenotypic difference between these two individuals and the size of the deleted region does not generally predict clinical features. Little is currently known about these genes complicating a direct genotype/phenotype correlation at this time. These data however, suggest that ZMYND11 and/or DIP2C haploinsufficiency contributes to the clinical features associated with 10p15 deletions in probands described in this study., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2012
- Full Text
- View/download PDF
24. Beckwith-Wiedemann syndrome in sibs discordant for IC2 methylation.
- Author
-
Niederhoffer KY, Peñaherrera M, Pugash D, Rupps R, Arbour L, Tessier F, Choufani S, Zhao C, Manokhina I, Shuman C, Robinson WP, Weksberg R, and Boerkoel CF
- Subjects
- Child, Child, Preschool, Chromosomes, Human, Pair 11, Humans, Infant, Male, Microsatellite Repeats, Beckwith-Wiedemann Syndrome genetics, DNA Methylation, Genomic Imprinting
- Abstract
Genetically heterogeneous imprinting disorders include Beckwith-Wiedemann syndrome (BWS) and multiple maternal hypomethylation syndrome (MMHS). Using DNA sequencing, quantitative PCR, SNuPE, pyrosequencing, and hybridization to the Illumina GoldenGate Methylation Cancer Panel 1 array, we characterized the genomic DNA of two brothers with BWS who were discordant for loss of methylation at several differentially methylated regions (DMR), including imprinting center 2 (IC2) on chromosome band 11p15.5, which is often hypomethylated in BWS. In keeping with MMHS, the elder child had hypomethylation of SGCE and PLAGL1 as well as of IC2, whereas the younger brother demonstrated no loss of methylation at these DMRs. Although this discordance is consistent with the observation that 15-20% of individuals with BWS do not have detectable genetic or epigenetic alterations of 11p15.5, this is the first report of familial recurrence of BWS with discordance for chromosomal 11p15.5 alterations. We hypothesize that this apparent discordance arises either from mosaicism precluding identification of IC2 hypomethylation in blood or buccal mucosa DNA of the younger child, or from hypomethylation at a site not interrogated by our molecular studies., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2012
- Full Text
- View/download PDF
25. An analysis of exome sequencing for diagnostic testing of the genes associated with muscle disease and spastic paraplegia.
- Author
-
Dias C, Sincan M, Cherukuri PF, Rupps R, Huang Y, Briemberg H, Selby K, Mullikin JC, Markello TC, Adams DR, Gahl WA, and Boerkoel CF
- Subjects
- Calpain genetics, Female, Humans, Muscle Proteins genetics, Muscular Dystrophies, Limb-Girdle genetics, Mutation, Polymorphism, Single Nucleotide, Young Adult, Exome, Muscular Diseases genetics, Paraplegia genetics, Sequence Analysis, DNA methods
- Abstract
In this study, we assess exome sequencing (ES) as a diagnostic alternative for genetically heterogeneous disorders. Because ES readily identified a previously reported homozygous mutation in the CAPN3 gene for an individual with an undiagnosed limb girdle muscular dystrophy, we evaluated ES as a generalizable clinical diagnostic tool by assessing the targeting efficiency and sequencing coverage of 88 genes associated with muscle disease (MD) and spastic paraplegia (SPG). We used three exome-capture kits on 125 individuals. Exons constituting each gene were defined using the UCSC and CCDS databases. The three exome-capture kits targeted 47-92% of bases within the UCSC-defined exons and 97-99% of bases within the CCDS-defined exons. An average of 61.2-99.5% and 19.1-99.5% of targeted bases per gene were sequenced to 20X coverage within the CCDS-defined MD and SPG coding exons, respectively. Greater than 95-99% of targeted known mutation positions were sequenced to ≥1X coverage and 55-87% to ≥20X coverage in every exome. We conclude, therefore, that ES is a rapid and efficient first-tier method to screen for mutations, particularly within the CCDS annotated exons, although its application requires disclosure of the extent of coverage for each targeted gene and supplementation with second-tier Sanger sequencing for full coverage., (© 2012 Wiley Periodicals, Inc.)
- Published
- 2012
- Full Text
- View/download PDF
26. Hypothesis: SLC12A3 Polymorphism modifies thiazide hypersensitivity of antenatal Bartter syndrome to thiazide resistance.
- Author
-
Mammen C, Rupps R, Trnka P, and Boerkoel CF
- Subjects
- Bartter Syndrome, Child, Preschool, Diuretics, Gitelman Syndrome genetics, Heterozygote, Humans, Hypersensitivity, Male, Sodium-Potassium-Chloride Symporters, Solute Carrier Family 12, Member 3, Drug Resistance genetics, Polymorphism, Genetic, Receptors, Drug genetics, Symporters genetics, Thiazides pharmacology
- Abstract
We report a 5-year-old boy with thiazide-resistant Bartter syndrome. This is highly unusual since thiazide hypersensitivity is a common diagnostic finding in Bartter syndrome patients. Subsequent molecular testing identified compound heterozygosity for two novel mutations in KCNJ1, (c.556A > G and c.683G > A) which is associated with Bartter syndrome, and a paternally inherited polymorphism in SLC12A3 (c.791G > C). Mutations in SLC12A3 cause the thiazide-resistant tubulopathy Gitelman syndrome. Based on published studies of this polymorphism in SLC12A3 and the features of the proband's father, we postulate that this polymorphism modifies the phenotype of Bartter syndrome in the proband to thiazide resistance., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
27. Fetal alcohol syndrome: a phenocopy of spondylocarpotarsal synostosis syndrome?
- Author
-
Vassel J, Rupps R, Krakow D, Puvanachandra N, Gardiner JA, Lazeo SR, and Boerkoel CF
- Subjects
- Contractile Proteins genetics, Female, Fetal Alcohol Spectrum Disorders diagnostic imaging, Filamins, Humans, Infant, Newborn, Microfilament Proteins genetics, Mutation, Pregnancy, Radiography, Syndrome, Fetal Alcohol Spectrum Disorders pathology, Synostosis pathology, Tarsal Bones abnormalities
- Published
- 2010
- Full Text
- View/download PDF
28. A KCNQ1 V205M missense mutation causes a high rate of long QT syndrome in a First Nations community of northern British Columbia: a community-based approach to understanding the impact.
- Author
-
Arbour L, Rezazadeh S, Eldstrom J, Weget-Simms G, Rupps R, Dyer Z, Tibbits G, Accili E, Casey B, Kmetic A, Sanatani S, and Fedida D
- Subjects
- Animals, British Columbia epidemiology, Humans, Indians, North American ethnology, KCNQ1 Potassium Channel metabolism, Long QT Syndrome ethnology, Mice, Patch-Clamp Techniques, Pedigree, Sequence Analysis, DNA, Genetic Predisposition to Disease genetics, Indians, North American genetics, KCNQ1 Potassium Channel genetics, Long QT Syndrome epidemiology, Long QT Syndrome genetics, Mutation, Missense genetics
- Abstract
Purpose: Hereditary long QT syndrome is named for a prolonged QT interval reflecting predisposition to ventricular arrhythmias and sudden death. A high rate in a remote, northern Canadian First Nations community was brought to attention., Methods: Two severely affected index cases and 122 relatives were ascertained using community-based participatory research principles. Genetic sequencing of five known genes responsible for long QT syndrome was carried out on the index cases, leading to the identification of a novel missense mutation. Functional properties of the identified mutation were studied in transfected mouse ltk- cells using whole cell patch clamp techniques. Corrected QT interval measurements were obtained from participants and subsequent genotyping of relatives was carried out., Results: In the two index cases, a novel missense mutation (V205M) was identified in the S3 transmembrane helix of KvLQT1, the pore forming domain of the IKs channel complex. In transfected mouse ltk-cells the V205M mutation suppressed IKs by causing a dramatic depolarizing shift in activation voltage coupled with acceleration of channel deactivation. Twenty-two mutation carriers had a significantly higher mean corrected QT interval than noncarriers (465 +/- 28 milliseconds vs. 434 +/- 26 milliseconds, P < 0.0001); however, 30% of carriers had a corrected QT interval below 440 milliseconds., Conclusion: A novel KCNQ1 mutation in this founder population likely confers increased susceptibility to arrhythmias because of decreased IKs current. Even with a common mutation within a relatively homogenous population, clinical expression remains variable, exemplifying the multifactorial nature of long QT syndrome, and supporting the difficulty of definitive diagnosis without genetic testing. A community participatory approach enabled a comprehensive evaluation of the impact.
- Published
- 2008
- Full Text
- View/download PDF
29. Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders.
- Author
-
Michalk A, Stricker S, Becker J, Rupps R, Pantzar T, Miertus J, Botta G, Naretto VG, Janetzki C, Yaqoob N, Ott CE, Seelow D, Wieczorek D, Fiebig B, Wirth B, Hoopmann M, Walther M, Körber F, Blankenburg M, Mundlos S, Heller R, and Hoffmann K
- Subjects
- Animals, Genes, Recessive genetics, Humans, In Situ Hybridization, Mice, Models, Biological, Muscle, Skeletal metabolism, Mutation genetics, Myasthenic Syndromes, Congenital embryology, Pedigree, Abnormalities, Multiple genetics, Fetal Diseases genetics, Myasthenic Syndromes, Congenital genetics, Receptors, Cholinergic genetics, Receptors, Nicotinic genetics
- Abstract
Impaired fetal movement causes malformations, summarized as fetal akinesia deformation sequence (FADS), and is triggered by environmental and genetic factors. Acetylcholine receptor (AChR) components are suspects because mutations in the fetally expressed gamma subunit (CHRNG) of AChR were found in two FADS disorders, lethal multiple pterygium syndrome (LMPS) and Escobar syndrome. Other AChR subunits alpha1, beta1, and delta (CHRNA1, CHRNB1, CHRND) as well as receptor-associated protein of the synapse (RAPSN) previously revealed missense or compound nonsense-missense mutations in viable congenital myasthenic syndrome; lethality of homozygous null mutations was predicted but never shown. We provide the first report to our knowledge of homozygous nonsense mutations in CHRNA1 and CHRND and show that they were lethal, whereas novel recessive missense mutations in RAPSN caused a severe but not necessarily lethal phenotype. To elucidate disease-associated malformations such as frequent abortions, fetal edema, cystic hygroma, or cardiac defects, we studied Chrna1, Chrnb1, Chrnd, Chrng, and Rapsn in mouse embryos and found expression in skeletal muscles but also in early somite development. This indicates that early developmental defects might be due to somite expression in addition to solely muscle-specific effects. We conclude that complete or severe functional disruption of fetal AChR causes lethal multiple pterygium syndrome whereas milder alterations result in fetal hypokinesia with inborn contractures or a myasthenic syndrome later in life.
- Published
- 2008
- Full Text
- View/download PDF
30. Congenital heart defects in Canadian Inuit: is more folic acid making a difference?
- Author
-
Arbour L, Rupps R, MacDonald S, Forth M, Yang J, Nowdluk M, and Osborne G
- Subjects
- Adolescent, Adult, Canada epidemiology, Case-Control Studies, Female, Folic Acid blood, Food, Fortified, Heart Defects, Congenital prevention & control, Humans, Male, Middle Aged, Risk Factors, Folic Acid therapeutic use, Heart Defects, Congenital epidemiology, Inuit
- Abstract
Introduction: Grain fortification of flour with folic acid has successfully reduced neural tube defects (NTDs) by approximately one half of the pre-fortification rate. The knowledge that the use of multivitamins with folic acid has also been shown to reduce some birth defects has prompted interest in determining whether folic acid may also play a role in the prevention of non-neural tube defects. Although NTDs are not more frequent in the Inuit of the Eastern Arctic, septal heart defects, were documented pre-fortification (1989-1994) to be increased 4 fold., Objectives: To determine if current efforts of fortification are sufficient and to explore other genetic/ environmental determinants of the increased rate of septal heart defects in the Eastern Arctic., Methods: Inuit mothers of children from communities on Baffin Island with and without heart defects were invited to participate in a case control study evaluating nutrient intake, pregnancy exposures, RBC folate, serum cobalamin, homocysteine, and functional polymorphisms for genes important in folate metabolism and uptake., Results: 41 children with isolated heart defects and their mothers with 36 community matched Inuit controls have entered the study to date., Results: There were no differences in RBC folate (953 Vs 922 nmol/L p = .49), serum cobalamin, and homocysteine, between mothers of cases and controls. The combined average RBC folate for the women ages 18-45 was 947 +/- 32 nmol/L. There was no difference between any documented alcohol (H"30%) and cigarette (H"82%) use in pregnancy. No Inuit women were taking vitamins at conception or at the time of this study. The results of the genetic studies will be reported elsewhere., Conclusions: RBC folate (post-fortification) in our sample of women of childbearing years is reassuring. However, it is possible that pre-fortification levels combined with genetic predisposition may have previously influenced the high rate of heart defects. Follow-up study is underway to determine if rates of heart defects have decreased since fortification was commenced. Since folate alone may not be sufficient to reduce non-neural tube defects, culturally appropriate public health efforts need to be initiated to encourage multivitamin use periconceptionally.
- Published
- 2007
31. Characteristics of primary biliary cirrhosis in British Columbia's First Nations population.
- Author
-
Arbour L, Rupps R, Field L, Ross P, Erikson A, Henderson H, Hill W, and Yoshida E
- Subjects
- Adult, Autoimmune Diseases ethnology, British Columbia epidemiology, Comorbidity, Genetic Predisposition to Disease, Humans, Liver Cirrhosis, Biliary diagnosis, Liver Cirrhosis, Biliary genetics, Liver Transplantation, Middle Aged, Pedigree, Referral and Consultation statistics & numerical data, Indians, North American, Liver Cirrhosis, Biliary ethnology
- Abstract
Unlabelled: Primary biliary cirrhosis (PBC) is a rare, autoimmune liver disorder characterized by progressive destruction of intrahepatic bile ducts, that results in portal inflammation, scarring, cirrhosis and, eventually, liver failure. Although considered rare in Canadian populations, it is the leading indication for referral for liver transplantation in British Columbia's First Nations population. Previously, an expanded review of all cases referred to the British Columbia Transplant Society for PBC was carried out comparing the demographics of those of First Nations descent with those not of First Nations descent. The review suggested that the rate of referral for transplantation was eight times higher for those of First Nations descent compared with those of other descent (P=0.0001), and a disproportionate number of the First Nations cases lived on Vancouver Island (48% of cases versus 18% expected, P<0.05). Additionally, the age of referral was significantly younger (45.9 versus 54.3 years) for those of First Nations descent and there are fewer First Nations men referred (1:34) than expected. For the purpose of the present report, 28 symptomatic cases were ascertained separately and reviewed in a clinical study to delineate the features of this population., Results: Although available liver biopsy reports were consistent with PBC, not all cases were antimitochondrial antibody-positive (18% negative). There was a family history of PBC confirmed by medical records in 33% of cases. There were five multiplex families identified, one with seven affected individuals. Detailed family histories revealed a recurrence risk of 4% for PBC for all first-degree relatives older than 21 years of age, but 10% when considering only women. Other autoimmune conditions coexisted in PBC patients in 79% of all cases. Arthritis was most frequent (60%), with thyroid disease (16%) and systemic lupus erythematosus (12%) also present. Additionally, a history of autoimmune diseases (arthritis, systemic lupus erythematosus and thyroid disease) was present in 21% of first-degree relatives. A strong genetic predisposition to PBC and other autoimmune diseases, combined with common environmental factors, is postulated in this population. Further study is underway to identify these factors.
- Published
- 2005
- Full Text
- View/download PDF
32. Renal-coloboma syndrome: prenatal detection and clinical spectrum in a large family.
- Author
-
Ford B, Rupps R, Lirenman D, Van Allen MI, Farquharson D, Lyons C, and Friedman JM
- Subjects
- Adolescent, Adult, Aged, Child, DNA-Binding Proteins genetics, Female, Fetal Death, Fetus abnormalities, Fundus Oculi, Humans, Infant, Newborn, Kidney abnormalities, Male, Middle Aged, PAX2 Transcription Factor, Pedigree, Pregnancy, Syndrome, Transcription Factors genetics, Coloboma diagnosis, Coloboma genetics, Urogenital Abnormalities genetics
- Abstract
Renal-coloboma syndrome includes abnormalities in the urogenital and ocular systems as its primary manifestations, although it can be associated with abnormalities in other systems as well. This syndrome is caused by mutations in the PAX2 gene and is transmitted as an autosomal dominant trait. We report a family in which at least 7 members have manifestations of renal-coloboma syndrome, including two in whom renal disease was diagnosed prenatally by ultrasound examination. A pathogenic frame-shift mutation (619insG) was found in the PAX2 gene in affected family members, who show remarkable variability in both the ocular and renal manifestations of the syndrome., (Copyright 2001 Wiley-Liss, Inc.)
- Published
- 2001
- Full Text
- View/download PDF
33. Recurrent trisomy 21 in a couple with a child presenting trisomy 21 mosaicism and maternal uniparental disomy for chromosome 21 in the euploid cell line.
- Author
-
Bruyère H, Rupps R, Kuchinka BD, Friedman JM, and Robinson WP
- Subjects
- Child, Female, Humans, Meiosis genetics, Recurrence, Chromosomes, Human, Pair 21, Down Syndrome genetics, Mosaicism genetics
- Abstract
Recurrence of trisomy 21 was observed in a family in which both parents had a normal chromosome complement. Mosaic trisomy 21 was found in a blood karyotype of the first child, a second pregnancy ended in spontaneous abortion, and a full trisomy 21 was found at prenatal diagnosis of the third pregnancy of this same couple. Although recurrent trisomy 21 may be due to chance, the possibility of germline mosaicism for trisomy 21 in one of the parents has important implications for recurrence risk. Molecular analysis was therefore undertaken in this family to determine the parental origin and the stage of nondisjunction of the extra chromosome 21 in both cases. Although a maternal origin of both instances of trisomy 21 was observed, the mosaic case showed homozygosity for all markers along the duplicated maternal chromosome. Such a finding would normally suggest a postzygotic origin of the trisomy 21. However, the diploid cell line in this same case showed maternal uniparental disomy 21, implying that it was the result of a trisomic conception. We suggest that a somatic nondisjunction in the maternal germ cells is the most likely explanation for these findings. The apparent meiotic II stage of nondisjunction of the nonmosaic trisomy 21 fetus was consistent with maternal mosaicism. A review of the literature for recurrent trisomy 21 cases studied by molecular means, suggests that mosaicism in germ cells may account for more cases than is detected cytogenetically. These results also show that DNA marker analysis does not provide a valuable tool for patient counseling in case of recurrent trisomy 21., (Copyright 2000 Wiley-Liss, Inc.)
- Published
- 2000
- Full Text
- View/download PDF
34. Skeletal and cardiac malformations with thrombocytopenia: a new syndrome?
- Author
-
Rupps R, Elliott AM, Azouz EM, Bernstein ML, Kaplan P, Eydoux P, and Der Kaloustian VM
- Subjects
- Carpal Bones abnormalities, Child, Developmental Disabilities, Female, Humans, Spine abnormalities, Syndrome, Abnormalities, Multiple, Heart Septal Defects, Atrial, Heart Septal Defects, Ventricular, Thrombocytopenia congenital
- Abstract
We describe a female patient with multiple anomalies suggestive of a new syndrome. Manifestations include: VSD and ASD, mild developmental delay, conductive hearing loss, minor facial anomalies, thrombocytopenia, and radiological findings (including carpal fusion). Some of these manifestations may be present in the Keutel syndrome, IVIC syndrome, and the 10qter deletion syndrome. However, none of these syndromes can explain the spectrum of anomalies seen in our patient.
- Published
- 1996
- Full Text
- View/download PDF
35. Increased permeability of lymphatic trunks draining granulomas.
- Author
-
Carr J, Carr I, and Rupps R
- Subjects
- Animals, Epithelium ultrastructure, Freund's Adjuvant, Granuloma pathology, Histamine pharmacology, Male, Permeability, Rats, Serotonin pharmacology, p-Methoxy-N-methylphenethylamine pharmacology, Granuloma physiopathology, Lymphatic System physiopathology, Lymphatic System ultrastructure
- Published
- 1980
36. [Early development of schizophrenic patients. An anamnestic study (author's transl)].
- Author
-
Keppler K, Lempp R, Paschedag D, Rebmann HE, and Rupps R
- Subjects
- Adult, Diseases in Twins, Female, Humans, Infant, Male, Medical History Taking, Pregnancy, Schizophrenia genetics, Social Environment, Twins, Monozygotic, Personality Development, Schizophrenia diagnosis
- Published
- 1979
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.