Alport syndrome and leiomyomatosis: the first deletion extending beyond COL4A6 intron 2
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Vera Uliana & Elena Marcocci & Mafalda Mucciolo & Ilaria Meloni & Claudia Izzi & Carlo Manno & Mirella Bruttini & Francesca Mari & Francesco Scolari
- چاپ و سال / کشور: 2011
Description
Alport syndrome (ATS) is a nephropathy characterized by the association of progressive hematuric nephritis with ultrastructural changes of the glomerular basement membrane (thinning, thickening, and splitting), sensorineural deafness, and variable ocular abnormalities (anterior lenticonus, macular flecks, and cataracts). The most common mode of transmission is X-linked inheritance, due to COL4A5 mutations. X-linked ATS is rarely associated with diffuse leiomyomatosis (DL), a benign hypertrophy of the visceral smooth muscle in gastrointestinal, respiratory, and female reproductive tracts. The ATSDL complex is due to deletions that encompass the 5پŒ ends of the COL4A5 and COL4A6 genes and include the bidirectional promoter. In this paper, we described 3 ATSDL cases, 2 familial and 1 sporadic bearing a deletion encompassing the 5پŒ-end of both the COL4A5 and COL4A6 genes, as identified by multiplex ligation-dependent probe amplification (MLPA) analysis. The array-CGH technique allowed a better definition of deletion size, confirming that the proximal breakpoint was within COL4A6 intron 2 in 2 cases. Surprisingly, 1 case had a deletion extending proximally beyond exon 3 of COL4A6, as confirmed by qPCR analysis. This is the largest deletion reported to date that has been associated with ATS-DL and this case should lead us to reconsider the mechanisms that might be involved in the development of diffuse leiomyomatosis.
Pediatr Nephrol (2011) 26:717–724 DOI 10.1007/s00467-010-1693-9 Received: 9 December 2009 / Revised: 20 September 2010 / Accepted: 23 September 2010 / Published online: 14 December 2010
