Deletion of the 5 ' exons of COL4A6 is not needed for the development of diffuse leiomyomatosis in patients with Alport syndrome

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Nabais Sa, MJN (Author) Other; Fieremans, N (Author) Other; de Brouwer, APM (Author) Other; Sousa, R (Author) Other; Teixeira e Costa, FTE (Author) Other; Brito, MJ (Author) Other; Carvalho, F (Author) Other; Rodrigues, M (Author) Other; de Sousa, FT (Author) Other; Felgueiras, J (Author) Other; Neves, F (Author) Other; Carvalho, A (Author) Other; Ramos, U (Author) Other; Vizcaino, JR (Author) Other; Alves, S (Author) Other; carvalho, f (Author) FMUP; Froyen, G (Author) Other; João Paulo Oliveira (Author) FMUP

Journal

Title: Journal of Medical Genetics

Vol. 50

Pages: 745-753

ISSN: 0022-2593

Publisher: BMJ PUBLISHING GROUP

Indexing

ISI Web of Knowledge - 12 Citations

Scopus - 15 Citations

Other information

Authenticus ID: P-006-JNN

DOI: 10.1136/jmedgenet-2013-101670

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9