Mutational spectrum of type I collagen genes in Korean patients with osteogenesis imperfecta.
Mutations in the type I collagen genes COL1A1 and COL1A2 are responsible for the dominantly inherited connective tissue disorder osteogenesis imperfecta (OI). The severity of OI is diverse, ranging from perinatal lethality to a very mild phenotype that is characterized by normal stature and the absence of deformities. Although there have been several studies on the mutational spectra of COL1A1 and/or COL1A2 in Western populations, very few cases have been reported from Asia. In this study, we investigated 67 unrelated Korean probands with OI and used nucleotide sequence analysis to detect COL1A1 and COL1A2 mutations. Thirty-five different mutations were identified in the two genes, including 24 novel mutations. Among the 35 kinds of detected mutations, 15 were glycine substitutions (seven in COL1A1 and eight in COL1A2), one was a nonsense mutation, four were frameshift mutations in COL1A1, three were in-frame duplications in COL1A2, and 12 were splice site mutations (seven in COL1A1 and five in COL1A2). Until now, mutations in the COL1A1 and COL1A2 genes known to cause OI were unique and rarely repeated in other families. Interestingly, the c.982G>A (p.Gly328Ser) mutation in COL1A2 was found recurrently and was the causative mutation in five independent OI probands. Haplotype analysis of the COL1A2 gene revealed that four probands from five independent OI probands with c.982G>A (p.Gly328Ser) had a common haplotype. Our clinical data showed the heterogeneity even within a specific genotype, which suggested the complex expression of this disease.
Lee
Kwang-Soo
KS
Division of Genetic Disease, Department of Biomedical Sciences, National Institute of Health, Seoul, Korea.
Song
Hae-Ryong
HR
Cho
Tae-Joon
TJ
Kim
Hyon J
HJ
Lee
Tae-Mi
TM
Jin
Hyun-Seok
HS
Park
Hyun-Young
HY
Kang
Seongman
S
Jung
Sung-Chul
SC
Koo
Soo Kyung
SK
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D024042:Collagen Type I / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007723:Korea / Q000453:epidemiology; D008297:Male; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012326:RNA Splicing
D024042:Collagen Type I