Identification and molecular characterization of two novel mutations in COL1A2 in two Chinese families with osteogenesis imperfecta  

作　　者：Zhenping Xu Yulei Li Xiangyang Zhang Fanming Zeng Mingxiong Yuan Mugen Liu Qing Kenneth Wang Jing Yu Liu 

机构地区：[1]Key Laboratory of Molecular Biophysics of the Ministry of Education,Center for Human Genome Research,College of Life Science and Technology,Huazhong University of Science and Technology,Wuhan 430074,China [2]Key Open Laboratory for Tissue Regeneration of Henan Universities,Department of Life Science and Technique,Xinxiang Medical University,Xinxiang 453003,China [3]Department of Molecular Cardiology,Cleveland Clinic,Cleveland,OH 44195,USA

出　　处：《Journal of Genetics and Genomics》2011年第4期149-156,共8页遗传学报（英文版）

基　　金：supported by the China Natural Science Foundation grants (Nos. 30670736 and 30972655);the National Basic Research Program of China (973 Program) (No. 2007CB512002).

摘　　要：Osteogenesis imperfecta（OI,also known as brittle bone disease）is caused mostly by mutations in two type I collagen genes,COL1A1 and COLIA2 encoding the pro-α1（I）and pro-α2（I）chains of type I collagen,respectively.Two Chinese families with autosomal dominant OI were identified and characterized.Linkage analysis revealed linkage of both families to COL1A2 on chromosome 7q21.3-q22.1.Mutational analysis was carried out using direct DNA sequence analysis.Two novel missense mutations,c.3350AG and c.3305GC,were identified in exon 49 of COL1A2 in the two families,respectively.The c.3305GC mutation resulted in substitution of a glycine residue（G）by an alanine residue（A）at codon 1102（p.G1102A）,which was found to be mutated into serine（S）,argine（R）,aspartic acid（D）,or valine（V）in other families.The c.3350AG variant may be a de novo mutation resulting in p.Y1117C.Both mutations co-segregated with OI in respective families,and were not found in 100 normal controls.The G1102 and Y1117 residues were evolutionarily highly conserved from zebrafish to humans.Mutational analysis did not identify any mutation in the COX-2 gene（a modifier gene of OI）.This study identifies two novel mutations p.G1102A and p.Y1117C that cause OI,significantly expands the spectrum of COL1A2 mutations causing OI,and has a significant implication in prenatal diagnosis of OI.Osteogenesis imperfecta（OI,also known as brittle bone disease）is caused mostly by mutations in two type I collagen genes,COL1A1 and COLIA2 encoding the pro-α1（I）and pro-α2（I）chains of type I collagen,respectively.Two Chinese families with autosomal dominant OI were identified and characterized.Linkage analysis revealed linkage of both families to COL1A2 on chromosome 7q21.3-q22.1.Mutational analysis was carried out using direct DNA sequence analysis.Two novel missense mutations,c.3350AG and c.3305GC,were identified in exon 49 of COL1A2 in the two families,respectively.The c.3305GC mutation resulted in substitution of a glycine residue（G）by an alanine residue（A）at codon 1102（p.G1102A）,which was found to be mutated into serine（S）,argine（R）,aspartic acid（D）,or valine（V）in other families.The c.3350AG variant may be a de novo mutation resulting in p.Y1117C.Both mutations co-segregated with OI in respective families,and were not found in 100 normal controls.The G1102 and Y1117 residues were evolutionarily highly conserved from zebrafish to humans.Mutational analysis did not identify any mutation in the COX-2 gene（a modifier gene of OI）.This study identifies two novel mutations p.G1102A and p.Y1117C that cause OI,significantly expands the spectrum of COL1A2 mutations causing OI,and has a significant implication in prenatal diagnosis of OI.

关 键 词：Osteogenesis imperfecta MUTATION COL1A2 COX-2 

分 类 号：Q754[生物学—分子生物学] TS976[轻工技术与工程]