Four new cases of lethal osteogenesis imperfecta due to glycine substitutions in COL1A1 and genes

• Published in: Human mutation Vol. 12; no. 1; pp. 71 - 72
• Main Authors: Mottes, Monica, Lira, Macarena Gomez, Zolezzi, Francesca, Valli, Maurizia, Lisi, Veronica, Freising, Peter
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 1998; Hindawi Limited
• ISSN: 1059-7794; 1098-1004
• DOI: 10.1002/(SICI)1098-1004(1998)12:1<71::AID-HUMU16>3.0.CO;2-4

Perinatal lethal osteogenesis imperfecta is the result of heterozygous mutations of the COL1A1 and COL1A2 genes. Here we describe the molecular defects responsible for four cases of lethal OI. Two glycine substitutions within the COL1A1 gene (G478S, G994D) and two glycine substitutions within the COL1A2 gene (G319V, G697C) were identified. The mutation sites were localized in proalpha2(I)and proalpha2(I)mRNA molecules, respectively, by chemical cleavage of mismatch in heteroduplex nucleic acids. Subsequent reverse transcription‐ PCR amplification, cloning and sequencing, led to mutation identification. The amino acid substitutions were due to two G→A transitions in COL1A1(cases 1,2), to a G→T transversion in COL1A2 (case 3), and to two contiguous point mutations in COL1A2 (case 4). All five nucleotide changes appeared to be fresh mutations. COL1A1(accession number Z74615) and COL1A2 (accession number Z74616) wild type coding sequences (cDNA) were deduced from the EMBL DNA sequence database. The mutations described here can also be found in the human type I collagen mutation database at the web site: http://www.le.ac.uk/genetics/collagen. Hum Mutat 12;71–72, 1998. © 1998 Wiley‐Liss, Inc.