10 results on '"D'Urso, Michele"'
Search Results
2. Microdeletion/duplication at the Xq28 IP locus causes a de novo IKBKG/NEMO/IKKgamma exon4_10 deletion in families with Incontinentia Pigmenti.
- Author
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Fusco F, Paciolla M, Pescatore A, Lioi MB, Ayuso C, Faravelli F, Gentile M, Zollino M, D'Urso M, Miano MG, and Ursini MV
- Subjects
- Base Sequence, Family, Female, Humans, I-kappa B Kinase metabolism, Incontinentia Pigmenti metabolism, Male, Models, Genetic, Molecular Sequence Data, Pedigree, Chromosomes, Human, X genetics, Exons genetics, Gene Duplication, I-kappa B Kinase genetics, Incontinentia Pigmenti genetics, Sequence Deletion
- Abstract
The Incontinentia Pigmenti (IP) locus contains the IKBKG/NEMO/IKKgamma gene and its truncated pseudogene copy, IKBKGP/deltaNEMO. The major genetic defect in IP is a heterozygous exon4_10 IKBKG deletion (IKBKGdel) caused by a recombination between two consecutive MER67B repeats. We analyzed 91 IP females carrying the IKBKGdel, 59 of whom carrying de novo mutations (65%). In eight parents, we found two recurrent nonpathological variants of IP locus, which were also present as rare polymorphism in control population: the IKBKGPdel, corresponding to the exon4_10 deletion in the pseudogene, and the MER67Bdup, that replicates the exon4_10 region downstream of the normal IKBKG gene. Using quantitative DNA analysis and microsatellite mapping, we established that both variants might promote the generation of the pathological IKBKGdel. Indeed, in family IP-516, the exon4_10 deletion was repositioned in the same allele from the pseudogene to the gene, whereas in family IP-688, the MER67Bdup generated the pathological IKBKGdel by recombination between two direct nonadjacent MER67Bs. Moreover, we found an instance of somatic recombination in a MER67Bdup variant, creating the IKBKGdel in an IP male. Our data suggest that the IP locus undergoes recombination producing recurrent variants that might be "at risk" of generating de novo IKBKGdel by NAHR during either meiotic or mitotic division.
- Published
- 2009
- Full Text
- View/download PDF
3. MRX87 family with Aristaless X dup24bp mutation and implication for polyAlanine expansions.
- Author
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Laperuta C, Spizzichino L, D'Adamo P, Monfregola J, Maiorino A, D'Eustacchio A, Ventruto V, Neri G, D'Urso M, Chiurazzi P, Ursini MV, and Miano MG
- Subjects
- DNA Primers, Humans, Male, Mutation, Pedigree, Sequence Analysis, DNA, Chromosomes, Human, X, Gene Duplication, Genetic Linkage, Homeodomain Proteins genetics, Mental Retardation, X-Linked genetics, Peptides genetics, Transcription Factors genetics
- Abstract
Background: Cognitive impairments are heterogeneous conditions, and it is estimated that 10% may be caused by a defect of mental function genes on the X chromosome. One of those genes is Aristaless related homeobox (ARX) encoding a polyA-rich homeobox transcription factor essential for cerebral patterning and its mutations cause different neurologic disorders. We reported on the clinical and genetic analysis of an Italian family with X-linked mental retardation (XLMR) and intra-familial heterogeneity, and provided insight into its molecular defect., Methods: We carried out on linkage-candidate gene studies in a new MRX family (MRX87). All coding regions and exon-intron boundaries of ARX gene were analysed by direct sequencing., Results: MRX87 patients had moderate to profound cognition impairment and a combination of minor congenital anomalies. The disease locus, MRX87, was mapped between DXS7104 and DXS1214, placing it in Xp22-p21 interval, a hot spot region for mental handicap. An in frame duplication of 24 bp (ARXdup24) in the second polyAlanine tract (polyA_II) in ARX was identified., Conclusion: Our study underlines the role of ARXdup24 as a critical mutational site causing mental retardation linked to Xp22. Phenotypic heterogeneity of MRX87 patients represents a new observation relevant to the functional consequences of polyAlanine expansions enriching the puzzling complexity of ARXdup24-linked diseases.
- Published
- 2007
- Full Text
- View/download PDF
4. Heterozygosity mapping by quantitative fluorescent PCR reveals an interstitial deletion in Xq26.2-q28 associated with ovarian dysfunction.
- Author
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Fimiani G, Laperuta C, Falco G, Ventruto V, D'Urso M, Ursini MV, and Miano MG
- Subjects
- Adult, Chromosome Mapping, Female, Genetic Carrier Screening, Genotype, Humans, Karyotyping, Microsatellite Repeats, Pedigree, Polymerase Chain Reaction methods, X Chromosome Inactivation, Chromosome Deletion, Chromosomes, Human, X genetics, Menopause, Premature genetics, Primary Ovarian Insufficiency genetics
- Abstract
Background: Deletions of Xq chromosome are reported for a number of familial conditions exhibiting premature ovarian failure (POF) and early menopause (EM)., Methods and Results: We describe the inheritance of an interstitial deletion of the long arm of the X chromosome associated with either POF or EM in the same family. Cytogenetic studies and heterozygosity mapping by quantitative fluorescent PCR revealed a 46,X,del(X)(q26.2-q28) karyotype in a POF female, in her EM mother, and also in her aborted fetus with severe cardiopathy. Applying a microsatellite approach, we have narrowed the extension of an identical interstitial deletion located between DXS1187 and DXS1073. These data, in line with other mapped deletions, single out the proximal Xq28 as the region most frequently involved in ovarian failure. We also propose that other factors may influence the phenotypic effect of this alteration. Indeed, skewed X inactivation has been ascertained in EM and POF to be associated with different X haplotypes., Conclusion: Our analysis indicates that Xq26.2-q28 deletion is responsible for gonad dysgenesis in a family with EM/POF. The dissimilar deletion penetrance may be due to epigenetic modifications of other X genes that can contribute to human reproduction, highlighting that ovarian failure should be considered as a multifactorial disease.
- Published
- 2006
- Full Text
- View/download PDF
5. The DNA sequence of the human X chromosome.
- Author
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Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, Platzer M, Howell GR, Burrows C, Bird CP, Frankish A, Lovell FL, Howe KL, Ashurst JL, Fulton RS, Sudbrak R, Wen G, Jones MC, Hurles ME, Andrews TD, Scott CE, Searle S, Ramser J, Whittaker A, Deadman R, Carter NP, Hunt SE, Chen R, Cree A, Gunaratne P, Havlak P, Hodgson A, Metzker ML, Richards S, Scott G, Steffen D, Sodergren E, Wheeler DA, Worley KC, Ainscough R, Ambrose KD, Ansari-Lari MA, Aradhya S, Ashwell RI, Babbage AK, Bagguley CL, Ballabio A, Banerjee R, Barker GE, Barlow KF, Barrett IP, Bates KN, Beare DM, Beasley H, Beasley O, Beck A, Bethel G, Blechschmidt K, Brady N, Bray-Allen S, Bridgeman AM, Brown AJ, Brown MJ, Bonnin D, Bruford EA, Buhay C, Burch P, Burford D, Burgess J, Burrill W, Burton J, Bye JM, Carder C, Carrel L, Chako J, Chapman JC, Chavez D, Chen E, Chen G, Chen Y, Chen Z, Chinault C, Ciccodicola A, Clark SY, Clarke G, Clee CM, Clegg S, Clerc-Blankenburg K, Clifford K, Cobley V, Cole CG, Conquer JS, Corby N, Connor RE, David R, Davies J, Davis C, Davis J, Delgado O, Deshazo D, Dhami P, Ding Y, Dinh H, Dodsworth S, Draper H, Dugan-Rocha S, Dunham A, Dunn M, Durbin KJ, Dutta I, Eades T, Ellwood M, Emery-Cohen A, Errington H, Evans KL, Faulkner L, Francis F, Frankland J, Fraser AE, Galgoczy P, Gilbert J, Gill R, Glöckner G, Gregory SG, Gribble S, Griffiths C, Grocock R, Gu Y, Gwilliam R, Hamilton C, Hart EA, Hawes A, Heath PD, Heitmann K, Hennig S, Hernandez J, Hinzmann B, Ho S, Hoffs M, Howden PJ, Huckle EJ, Hume J, Hunt PJ, Hunt AR, Isherwood J, Jacob L, Johnson D, Jones S, de Jong PJ, Joseph SS, Keenan S, Kelly S, Kershaw JK, Khan Z, Kioschis P, Klages S, Knights AJ, Kosiura A, Kovar-Smith C, Laird GK, Langford C, Lawlor S, Leversha M, Lewis L, Liu W, Lloyd C, Lloyd DM, Loulseged H, Loveland JE, Lovell JD, Lozado R, Lu J, Lyne R, Ma J, Maheshwari M, Matthews LH, McDowall J, McLaren S, McMurray A, Meidl P, Meitinger T, Milne S, Miner G, Mistry SL, Morgan M, Morris S, Müller I, Mullikin JC, Nguyen N, Nordsiek G, Nyakatura G, O'Dell CN, Okwuonu G, Palmer S, Pandian R, Parker D, Parrish J, Pasternak S, Patel D, Pearce AV, Pearson DM, Pelan SE, Perez L, Porter KM, Ramsey Y, Reichwald K, Rhodes S, Ridler KA, Schlessinger D, Schueler MG, Sehra HK, Shaw-Smith C, Shen H, Sheridan EM, Shownkeen R, Skuce CD, Smith ML, Sotheran EC, Steingruber HE, Steward CA, Storey R, Swann RM, Swarbreck D, Tabor PE, Taudien S, Taylor T, Teague B, Thomas K, Thorpe A, Timms K, Tracey A, Trevanion S, Tromans AC, d'Urso M, Verduzco D, Villasana D, Waldron L, Wall M, Wang Q, Warren J, Warry GL, Wei X, West A, Whitehead SL, Whiteley MN, Wilkinson JE, Willey DL, Williams G, Williams L, Williamson A, Williamson H, Wilming L, Woodmansey RL, Wray PW, Yen J, Zhang J, Zhou J, Zoghbi H, Zorilla S, Buck D, Reinhardt R, Poustka A, Rosenthal A, Lehrach H, Meindl A, Minx PJ, Hillier LW, Willard HF, Wilson RK, Waterston RH, Rice CM, Vaudin M, Coulson A, Nelson DL, Weinstock G, Sulston JE, Durbin R, Hubbard T, Gibbs RA, Beck S, Rogers J, and Bentley DR
- Subjects
- Animals, Antigens, Neoplasm genetics, Centromere genetics, Chromosomes, Human, Y genetics, Contig Mapping, Crossing Over, Genetic genetics, Dosage Compensation, Genetic, Female, Genetic Linkage genetics, Genetics, Medical, Humans, Male, Polymorphism, Single Nucleotide genetics, RNA genetics, Repetitive Sequences, Nucleic Acid genetics, Sequence Homology, Nucleic Acid, Testis metabolism, Chromosomes, Human, X genetics, Evolution, Molecular, Genomics, Sequence Analysis, DNA
- Abstract
The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.
- Published
- 2005
- Full Text
- View/download PDF
6. Mapping of MRX81 in Xp11.2-Xq12 suggests the presence of a new gene involved in nonspecific X-linked mental retardation.
- Author
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Annunziata I, Lanzara C, Conte I, Zullo A, Ventruto V, Rinaldi MM, D'Urso M, Casari G, Ciccodicola A, and Miano MG
- Subjects
- 5-Aminolevulinate Synthetase genetics, Alleles, Centrosome ultrastructure, Chromosome Mapping, DNA Mutational Analysis, Databases as Topic, Ephrin-B1 genetics, Exons, Family Health, Female, Genotype, Haplotypes, Humans, Male, Models, Genetic, Nuclear Proteins genetics, Pedigree, Phosphoproteins genetics, Recombination, Genetic, Chromosomes, Human, X, Cytoskeletal Proteins, GTPase-Activating Proteins, Genetic Linkage, Lod Score, Mental Retardation, X-Linked genetics
- Abstract
X-linked nonspecific mental retardation (MRX) accounts for approximately 25% of mental retardation in males. A number of MRX loci have been mapped on the X chromosome, reflecting the complexity of gene action in central nervous system (CNS) specification and function. Eleven MRX genes have been identified, but many other causative loci remain to be refined to the single gene level. In 21 MRX families, the causative gene is located in the pericentromeric region; and we report here the identification by linkage analysis of a further such locus, MRX81. The new MRX locus was identified by two- and multi-point parametric analysis carried out on a large Italian family. Tight linkage of MRX81 to DNA markers ALAS2, DXS991, and DXS7132 was observed with a maximum LOD score of 3.43. Haplotype construction delineates an MRX81 critical region of 8 cM, the smallest MRX pericentromeric interval so far described, between DXS1039 and DXS1216, and placing it in Xp11.2-Xq12. So far, automated sequencing of two candidates in the region, the MRX gene oligophrenin (OPHN1) and the brain-specific ephrinB1 (EFNB1) gene, in DNA from affected males excluded their candidacy for MRX81, suggesting a novel disease gene., (Copyright 2003 Wiley-Liss, Inc.)
- Published
- 2003
- Full Text
- View/download PDF
7. Allelic inactivation of the pseudoautosomal gene SYBL1 is controlled by epigenetic mechanisms common to the X and Y chromosomes.
- Author
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Matarazzo MR, De Bonis ML, Gregory RI, Vacca M, Hansen RS, Mercadante G, D'Urso M, Feil R, and D'Esposito M
- Subjects
- Cell Line, Transformed, Chromatin genetics, CpG Islands genetics, DNA Methylation, Female, Fibroblasts chemistry, Fibroblasts metabolism, Fibroblasts virology, Gene Expression Regulation genetics, Genetic Carrier Screening, Herpesvirus 4, Human, Histones chemistry, Histones metabolism, Humans, Hybrid Cells, Lymphocytes chemistry, Lymphocytes metabolism, Lymphocytes virology, Male, Membrane Proteins biosynthesis, Promoter Regions, Genetic genetics, R-SNARE Proteins, Alleles, Chromosomes, Human, X genetics, Chromosomes, Human, Y genetics, Gene Silencing, Membrane Proteins genetics
- Abstract
On the human long-arm pseudoautosomal region (XqPAR), genes that are subject to inactivation are closely linked with those that escape. Genes subject to inactivation are not only silenced on the inactive X in females, but they are also inactivated on the Y chromosome in males. One of the genes subject to this unusual inactivation pattern is the synaptobrevin-like 1 gene (SYBL1). Previously we showed that its silencing on the inactive X and the Y allele involves DNA methylation. This study explores the molecular events associated with SYBL1 silencing and investigates their relationship. Promoter DNA methylation profiles were determined by bisulfite sequencing and immunoprecipitation experiments demonstrate that chromatin on the repressed Xi and the Y alleles has underacetylated histones H3 and H4 and H3-lysine 9 methylation. In addition, the inactive X and the Y allele were found to have a condensed chromatin conformation. In contrast, the expressed allele shows H3 and H4 acetylation, H3-lysine 4 methylation and a less compacted chromatin conformation. In ICF syndrome, a human disease affecting DNA methylation, SYBL1 escapes from silencing and this correlates with altered patterns of histone methylation and acetylation. Combined, our data suggest that specific combinations of histone methylation and acetylation are involved in the somatic maintenance of permissive and repressed chromatin states at SYBL1. Although it is unclear at present how this allele-specific silencing comes about, the data also indicate that the epigenetic features of the 'Y inactivation' of SYBL1 are mechanistically similar to those associated with X-chromosome inactivation.
- Published
- 2002
- Full Text
- View/download PDF
8. Microdeletion/duplication at the Xq28 IP locus causes a de novo IKBKG/NEMO/IKKgamma exon4_10 deletion in families with Incontinentia Pigmenti
- Author
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Paciolla Mariateresa, Lioi Maria Brigida, Zollino Marcella, Miano Maria Giuseppina, Gentile Mattia, Ayuso Carmen, Pescatore Alessandra, Fusco Francesca, D'Urso Michele, Ursini Matilde Valeria, and Faravelli Francesca
- Subjects
Male ,Pseudogene ,Molecular Sequence Data ,IKBKG ,CNV ,Locus (genetics) ,IKKgamma ,Biology ,NEMO ,Gene Duplication ,Gene duplication ,Genetics ,medicine ,Humans ,Family ,Incontinentia Pigmenti ,Allele ,Somatic recombination ,Genetics (clinical) ,Sequence Deletion ,Chromosomes, Human, X ,Base Sequence ,Models, Genetic ,Exons ,Incontinentia pigmenti ,medicine.disease ,I-kappa B Kinase ,Pedigree ,Xq28 ,Female - Abstract
The Incontinentia Pigmenti (IP) locus contains the IKBKG/NEMO/IKKgamma gene and its truncated pseudogene copy, IKBKGP/deltaNEMO. The major genetic defect in IP is a heterozygous exon4_10 IKBKG deletion (IKBKGdel) caused by a recombination between two consecutive MER67B repeats. We analyzed 91 IP females carrying the IKBKGdel, 59 of whom carrying de novo mutations (65%). In eight parents, we found two recurrent nonpathological variants of IP locus, which were also present as rare polymorphism in control population: the IKBKGPdel, corresponding to the exon4_10 deletion in the pseudogene, and the MER67Bdup, that replicates the exon4_10 region downstream of the normal IKBKG gene. Using quantitative DNA analysis and microsatellite mapping, we established that both variants might promote the generation of the pathological IKBKGdel. Indeed, in family IP-516, the exon4_10 deletion was repositioned in the same allele from the pseudogene to the gene, whereas in family IP-688, the MER67Bdup generated the pathological IKBKGdel by recombination between two direct nonadjacent MER67Bs. Moreover, we found an instance of somatic recombination in a MER67Bdup variant, creating the IKBKGdel in an IP male. Our data suggest that the IP locus undergoes recombination producing recurrent variants that might be ''at risk'' of generating de novo IKBKGdel by NAHR during either meiotic or mitotic division.
- Published
- 2009
9. Heterozygosity mapping by quantitative fluorescent PCR reveals an interstitial deletion in Xq26.2-q28 associated with ovarian dysfunction
- Author
-
Maria Giuseppina Miano, Michele D'Urso, Giorgia Fimiani, Matilde Valeria Ursini, Valerio Ventruto, Geppino Falco, Carmela Laperuta, Fimiani, Giorgia, Laperuta, Carmela, Falco, Geppino, Ventruto, Valerio, D'Urso, Michele, Ursini, Matilde Valeria, and Miano, Maria Giuseppina
- Subjects
Adult ,medicine.medical_specialty ,Premature ovarian failure syndrome ,endocrine system diseases ,Heterozygosity mapping ,Genotype ,Menopause, Premature ,Biology ,Primary Ovarian Insufficiency ,Polymerase Chain Reaction ,X-inactivation ,Loss of heterozygosity ,Xq26.2-Xq28 ,X Chromosome Inactivation ,medicine ,Humans ,Skewed X-inactivation ,X chromosome ,Genetics ,Chromosomes, Human, X ,Genetic Carrier Screening ,Rehabilitation ,Cytogenetics ,Obstetrics and Gynecology ,Chromosome Mapping ,Quantitative fluorescent PCR ,medicine.disease ,Penetrance ,female genital diseases and pregnancy complications ,Xq28 ,Premature ovarian failure ,Pedigree ,XCI ,Reproductive Medicine ,Karyotyping ,Female ,Chromosome Deletion ,Microsatellite Repeats - Abstract
Background: Deletions of Xq chromosome are reported for a number of familial conditions exhibiting premature ovarian failure (POF) and early menopause (EM). Methods and results: We describe the inheritance of an interstitial deletion of the long arm of the X chromosome associated with either POF or EM in the same family. Cytogenetic studies and heterozygosity mapping by quantitative fluorescent PCR revealed a 46,X,del(X)(q26.2-q28) karyotype in a POF female, in her EM mother, and also in her aborted fetus with severe cardiopathy. Applying a microsatellite approach, we have narrowed the extension of an identical interstitial deletion located between DXS1187 and DXS1073. These data, in line with other mapped deletions, single out the proximal Xq28 as the region most frequently involved in ovarian failure. We also propose that other factors may influence the phenotypic effect of this alteration. Indeed, skewed X inactivation has been ascertained in EM and POF to be associated with different X haplotypes. Conclusion: Our analysis indicates that Xq26.2-q28 deletion is responsible for gonad dysgenesis in a family with EM/POF. The dissimilar deletion penetrance may be due to epigenetic modifications of other X genes that can contribute to human reproduction, highlighting that ovarian failure should be considered as a multifactorial disease. © The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
- Published
- 2005
10. Mapping of MRX81 in Xp11.2-Xq12 suggests the presence of a new gene involved in nonspecific X-linked mental retardation
- Author
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Maria Michela Rinaldi, Carmela Lanzara, Valerio Ventruto, Michele D'Urso, Ida Annunziata, Alberto Zullo, Ivan Conte, Giorgio Casari, Alfredo Ciccodicola, Maria Giuseppina Miano, Annunziata, I, Lanzara, C, Conte, I, Zullo, A, Ventruto, V, Rinaldi, Mm, D'Urso, M, Casari, GIORGIO NEVIO, Ciecodicola, A, Miano, Mg, Annunziata, Ida, Lanzara, Carmela, Conte, Ivan, Zullo, Alberto, Ventruto, Valerio, Rinaldi, Maria Michela, D'Urso, Michele, Casari, Giorgio, Ciccodicola, Alfredo, and Miano, Maria Giuseppina
- Subjects
Male ,Genotype ,Genetic Linkage ,DNA Mutational Analysis ,Exon ,linkage genetico ,Locus (genetics) ,Ephrin-B1 ,Biology ,DNA Mutational Analysi ,Genetic linkage ,Haplotype ,Cytoskeletal Protein ,Humans ,Allele ,Malattia X-linked ,Gene ,Alleles ,Genetics (clinical) ,X chromosome ,Nuclear Protein ,Centrosome ,Family Health ,Recombination, Genetic ,Genetics ,Chromosomes, Human, X ,Models, Genetic ,GTPase-Activating Protein ,GTPase-Activating Proteins ,Nuclear Proteins ,Chromosome Mapping ,Exons ,Phosphoproteins ,Pedigree ,Cytoskeletal Proteins ,Ritardo mentale ,Haplotypes ,Databases as Topic ,Genetic marker ,Phosphoprotein ,Mental Retardation, X-Linked ,Female ,Lod Score ,5-Aminolevulinate Synthetase ,Human - Abstract
X-linked nonspecific mental retardation (MRX) accounts for similar to25% of mental retardation in males. A number of MRX loci have been mapped on the X chromosome, reflecting the complexity of gene action in central nervous system (CNS) specification and function. Eleven MRX genes have been identified, but many other causative loci remain to be refined to the single gene level. In 21 MRX families, the causative gene is located in the pericentromeric region; and we report here the identification by linkage analysis of a further such locus, MRX81. The new MRX locus was identified by two- and multi-point parametric analysis carried out on a large Italian family. Tight linkage of MRX81 to DNA markers ALAS2, DXS991, and DXS7132 was observed with a maximum LOD score of 3.43. Haplotype construction delineates an MRX81 critical region of 8 cM, the smallest MRX pericentromeric interval so far described, between DXS1039 and DXS1216, and placing it in Xp11.2-Xq12. So far, automated sequencing of two candidates in the region, the MRX gene oligophrenin (OPHN1) and the brain-specific ephrinB1 (EFNB1) gene, in DNA from affected males excluded their candidacy for MRX81, suggesting a novel disease gene. (C) 2003 Wiley-Liss, Inc.
- Published
- 2003
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