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Paternal mosaicism for a COL1A1 dominant mutation (α1 Ser‐415) causes recurrent osteogenesis imperfecta
Author(s) -
Mottes Monica,
Macarena Lira M. Gomez,
Valli Maurizia,
Scarano Gioacchino,
Lonardo Fortunato,
Forlino Antonella,
Cetta Giuseppe,
Pignatti Pier Franco
Publication year - 1993
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.1380020308
Subject(s) - proband , osteogenesis imperfecta , biology , germline mosaicism , mutation , point mutation , microbiology and biotechnology , germline , genetics , transition (genetics) , germline mutation , gene , anatomy
We describe a dominant point mutation in the COL1A1 gene causing extremely severe osteogenesis imperfecta (OI type II/III) which was detected in the dermal fibroblasts of a proband, diagnosed by ultrasonography at 24 weeks of gestation. Type I collagen secretion was reduced and proαl(I) chains were overmodified. The mutation was localised in one COL1A1 allele by chemical cleavage of mismatched bases in normal cDNA/proband's mRNA heteroduplexes, and identified by cloning and sequencing. A G‐to‐A transition which causes the Substitution of Gly‐415 with serine in the a α1(I) triple helical domain was found. The same mutation was detected in the father's spermatozoa and lymphocytes. Mosaicism in the father's germline explains the occurrence in the family of two additional OI pregnancies, which were documented by X‐ray and ultrasound investigations. © 1993 Wiley‐Liss, Inc.