title: Deletion of the 5'exons of COL4A6 is not needed for the development of diffuse leiomyomatosis in patients with Alport syndrome.
abstract: 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.
authors: Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal.
authors: Maria João Nabais
authors: MJ
authors: Sá
authors: Nathalie
authors: N
authors: Fieremans
authors: Arjan P M
authors: AP
authors: de Brouwer
authors: Rita
authors: R
authors: Sousa
authors: Fernando Teixeira
authors: FT
authors: e Costa
authors: Maria José
authors: MJ
authors: Brito
authors: Fernanda
authors: F
authors: Carvalho
authors: Márcia
authors: M
authors: Rodrigues
authors: Francisco Teixeira
authors: FT
authors: de Sousa
authors: Joana
authors: J
authors: Felgueiras
authors: Fernando
authors: F
authors: Neves
authors: Adelino
authors: A
authors: Carvalho
authors: Umbelina
authors: U
authors: Ramos
authors: José Ramón
authors: JR
authors: Vizcaíno
authors: Susana
authors: S
authors: Alves
authors: Filipa
authors: F
authors: Carvalho
authors: Guy
authors: G
authors: Froyen
authors: João Paulo
authors: JP
authors: Oliveira
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D024141:Collagen Type IV / Q000235:genetics*; D005091:Exons; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D018231:Leiomyomatosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009394:Nephritis, Hereditary / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D055815:Young Adult
chemical_list: C559044:COL4A6 protein, human; D024141:Collagen Type IV
keywords: Clinical genetics; Genetics; Molecular genetics; Oesophagus; Renal Medicine