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Variable clinical expression in a family with OI type IV due to deletion of three base pairs in COL1A1
Author(s) -
Lund Allan M.,
Schwartz Marianne,
Skovby Flemming
Publication year - 1996
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.1996.tb02379.x
Subject(s) - cyanogen bromide , osteogenesis imperfecta , exon , microbiology and biotechnology , type i collagen , genetics , biology , phenotype , peptide sequence , gene , endocrinology , anatomy
We have studied a family with autosomal dominant osteogenesis imperfecta (OI) type IV. Electrophoresis of collagen produced by cultured fibroblasts revealed a slower migrating population of collagen I. Cyanogen bromide peptide mapping localised the structural defect to the area of the αl(l)CB3 peptide. Subsequent sequencing revealed a deletion of nucleotides 1964–1966 in exon 27 of COL1A1. By means of restriction enzyme analysis, the deletion could be detected in all affected family members. This in‐frame deletion resulted in the removal of alanine‐438 and a Glu437Asp substitution in the proαl (I) collagen chain. Clinical variation was considerable among affected family members. The most consistent clinical features were reduced height and extraosseous manifestations of OI.