Deletion of the 5'exons of COL4A6 is not needed for the development of diffuse leiomyomatosis in patients with Alport syndrome
| العنوان: | Deletion of the 5'exons of COL4A6 is not needed for the development of diffuse leiomyomatosis in patients with Alport syndrome |
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| المؤلفون: | Fernando Neves, Guy Froyen, S. Alves, Umbelina Ramos, Maria João Nabais Sá, Márcia Rodrigues, Fernando Teixeira e Costa, Nathalie Fieremans, Adelino Carvalho, Arjan P.M. de Brouwer, Maria José Brito, Joana Felgueiras, Fernanda Carvalho, Rita de Sousa, Francisco Sousa, José Ramón Vizcaíno, Filipa Carvalho, João Paulo Oliveira |
| المساهمون: | Clinical sciences, Medical Genetics |
| المصدر: | Journal of Medical Genetics, 50, 11, pp. 745-53 Journal of Medical Genetics, 50, 745-53 |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Adult, Collagen Type IV, Male, medicine.medical_specialty, Genotype, Nephritis, Hereditary, Biology, urologic and male genital diseases, Young Adult, Exon, Nephritis, Hereditary/genetics, Leiomyomatosis, Molecular genetics, otorhinolaryngologic diseases, Genetics, medicine, Humans, Alport syndrome, Child, Genetics (clinical), Molecular pathology, Leiomyomatosis/genetics, Exons, Middle Aged, medicine.disease, Molecular biology, Collagen Type IV/genetics, Pedigree, Genetics and epigenetic pathways of disease DCN MP - Plasticity and memory [NCMLS 6], Genetic epidemiology, Child, Preschool, Medical genetics, Female, Gene Deletion |
| الوصف: | Background Alport syndrome (AS), a hereditary type IV collagen nephropathy, is a major cause of end-stage renal disease in young people. About 85% of the cases are X-linked (ATS), due to mutations in the COL4A5 gene. Rarely, families have a contiguous gene deletion comprising at least exon 1 of COL4A5 and the first exons of COL4A6 , associated with the development of diffuse leiomyomatosis (ATS-DL). We report three novel deletions identified in families with AS, one of which challenges the current concepts on genotype-phenotype correlations of ATS/ATS-DL. Methods In the setting of a multicentric study aiming to describe the genetic epidemiology and molecular pathology of AS in Portugal, three novel COL4A5 deletions were identified in two families with x-linked Alport syndrome (ATS) and in one family with ATS-DL. These mutations were initially detected by PCR and Multiplex Ligation-dependent Probe Amplification, and further mapped by high-resolution X chromosome-specific oligo-array and PCR. Results In the ATS-DL family, a COL4A5 deletion spanning exons 2 through 51, extending distally beyond COL4A5 but proximally not into COL4A6 , segregated with the disease phenotype. A COL4A5 deletion encompassing exons 2 through 29 was identified in one of the ATS families. In the second ATS family, a deletion of exon 13 of COL4A5 through exon 3 of COL4A6 was detected. Conclusions These observations suggest that deletion of the 5′ exons of COL4A6 and of the common promoter of the COL4A5 and COL4A6 genes is not essential for the development of leiomyomatosis in patients with ATS, and that COL4A5_COL4A6 deletions extending into COL4A6 exon 3 may not result in ATS-DL. |
| تدمد: | 0022-2593 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6787d3c1f1221c4401d067104f30a7f2 https://doi.org/10.1136/jmedgenet-2013-101670 |
| حقوق: | RESTRICTED |
| رقم الأكسشن: | edsair.doi.dedup.....6787d3c1f1221c4401d067104f30a7f2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00222593 |
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