LINE-1 elements at the sites of molecular rearrangements in Alport syndrome-diffuse leiomyomatosis

Am J Hum Genet. 1999 Jan;64(1):62-9. doi: 10.1086/302213.


Deletions encompassing the 5' termini of the paired type IV collagen genes COL4A5 and COL4A6 on chromosome Xq22 give rise to Alport syndrome (AS) and associated diffuse leiomyomatosis (DL), a syndrome of disseminated smooth-muscle tumors involving the esophagus, large airways, and female reproductive tract. In this study, we report isolation and characterization of two deletion junctions. The first, in a patient described elsewhere, arose by a nonhomologous recombination event fusing a LINE-1 (L1) repetitive element in intron 1 of COL4A5 to intron 2 of COL4A6, resulting in a 13.4-kb deletion. The second, in a previously undescribed family, arose by unequal homologous recombination between the same L1 and a colinear L1 element in intron 2 of COL4A6, resulting in a>40-kb deletion. L1 elements have contributed to the emergence of this locus as a site of frequent recombinations by diverse mechanisms. These give rise to AS-DL by disruption of type IV collagen and perhaps other as yet unidentified genes, evidenced by deletions as small as 13.4 kb.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Base Sequence
  • Biopsy
  • Collagen / genetics
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunophenotyping
  • Long Interspersed Nucleotide Elements*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Nephritis, Hereditary / genetics*
  • Nephritis, Hereditary / immunology
  • Nephritis, Hereditary / pathology
  • Pedigree
  • Skin / pathology
  • X Chromosome*


  • Collagen

Associated data

  • GENBANK/U93574