The deafness-dystonia syndrome(DDS) is also known as Mohr-Tranebjaerg syndrome (MTS,MIM 304700).It is a rare X...
Cheng Wang1,Yulei Li1,Jun Yu Luo2,Jing Yu Liu(1) 1.College of Life Science and Technology,Huazhong University of Science and Technology,Wuhan,Hubei, 430074,P.R.China 2.Affiliated Secondary School,Huazhong University of Science and Technology,Wuhan,Hubei, 430074,P.R.China
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.
