A two-tier approach to mutation detection in the COL4A5 gene for Alport syndrome

• Published in: Human mutation Vol. 27; no. 10; p. 1061
• Main Authors: King, Kathy, Flinter, Frances A., Green, Peter M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-10-2006; Hindawi Limited
• Subjects: Alport syndrome; Base Sequence; chemical cleavage; Collagen Type IV - genetics; DHPLC; DNA Mutational Analysis - methods; Exons - genetics; Female; Frameshift Mutation - genetics; Humans; Male; Molecular Sequence Data; Mutation - genetics; mutation screening; Mutation, Missense - genetics; Nephritis, Hereditary - genetics; Nephritis, Hereditary - pathology; Sequence Deletion - genetics
• ISSN: 1059-7794; 1098-1004
• DOI: 10.1002/humu.9453

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.