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A two‐tier approach to mutation detection in the COL4A5 gene for Alport syndrome
Author(s) -
King Kathy,
Flinter Frances A.,
Green Peter M.
Publication year - 2006
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9453
Subject(s) - alport syndrome , biology , exon , missense mutation , genetics , mutation , gene , splice site mutation , mutation rate , gene mutation , microbiology and biotechnology , alternative splicing , glomerulonephritis , kidney
About 85% of Alport syndrome is an X‐linked semi‐dominant condition caused by mutations in the collagen gene, COL4A5 . The large size and high GC content of this gene have presented diagnostic laboratories with problems in identifying mutations with greater than about a 50% success rate since the gene was first cloned 16 years ago. An RNA based approach is adopted here for a first pass mutation scanning coupled with more traditional exon‐by‐exon screening to increase the rate of mutation identification. Twenty‐one mutations were identified in twenty‐five patients with clear Alport syndrome including four gross deletions, two deep intronic mutations, three frameshifts, three splice site mutations, eight missense mutations and one inframe deletion. © 2006 Wiley‐Liss, Inc.