Tags

Type your tag names separated by a space and hit enter

A novel RNA-splicing mutation in COL1A1 gene causing osteogenesis imperfecta type I in a Chinese family.
Clin Chim Acta. 2008 Dec; 398(1-2):148-51.CC

Abstract

BACKGROUND

Osteogenesis imperfecta (OI), also known as brittle bone disease, is a rare heterogeneous group of inherited disorders characterized by low bone mass and increased bone fragility. The four major clinical criteria for diagnosis of OI are osteoporosis with abnormal fragility of the skeleton, blue sclera, dentinogenesis imperfecta, and premature otosclerosis. The presence of two of these abnormalities confirms the diagnosis. More than 90% patients have autosomal dominant mutations in one of the two genes, COL1A1 and COL1A2, that encode the alpha chains of type I collagen. While the diagnosis of OI is still based on clinical and radiological grounds, there is a growing demand for the molecular characterization of causative mutations. 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. The purpose of this study is to report two patients with OI type I in a Chinese family, who had a novel RNA-splicing mutation in COL1A1 gene and describe the molecular, radiological and clinical findings.

METHODS

The proband, (case II-5), a 32-y-old Chinese male, and his 7-y-old daughter were diagnosed as OI type I according to their clinical and radiological features. Genomic DNA was extracted from their blood samples and all promoters, exons and exon/intron boundaries of COL1A1 and COL1A2 genes were sequenced. Polymerase chain reaction sequence-specific primers (PCR-SSP) was used to confirm patients' heterozygous state.

RESULTS

Direct DNA sequencing analysis of COL1A1 gene revealed a splicing mutation (c.1875+1G>A, also as IVS 27+1G>A) that converted the 5' end of intron 27 from GT to AT. This mutation was found in both 2 affected individuals but 9 unaffected relatives and the 50 controls were not observed, which was consistent with the clinical diagnosis. This mutation (c.1875+1G>A) appeared to be novel, which is neither reported in literature nor registered in the Database of Collagen Mutations. The heterozygous states of patients' intron 27 were confirmed by PCR-SSP.

CONCLUSION

We identify a novel RNA-splicing mutation (c.1875+1G>A) in COL1A1 gene resulting in OI type I in a Chinese family. The detailed molecular and clinical features will be useful for extending the evidence for genetic and phenotypic heterogeneity in OI and exploring the phenotype-genotype correlations in OI.

Authors+Show Affiliations

Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing 210002, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18755172

Citation

Xia, Xin-Yi, et al. "A Novel RNA-splicing Mutation in COL1A1 Gene Causing Osteogenesis Imperfecta Type I in a Chinese Family." Clinica Chimica Acta; International Journal of Clinical Chemistry, vol. 398, no. 1-2, 2008, pp. 148-51.
Xia XY, Cui YX, Huang YF, et al. A novel RNA-splicing mutation in COL1A1 gene causing osteogenesis imperfecta type I in a Chinese family. Clin Chim Acta. 2008;398(1-2):148-51.
Xia, X. Y., Cui, Y. X., Huang, Y. F., Pan, L. J., Yang, B., Wang, H. Y., Li, X. J., Shi, Y. C., Lu, H. Y., & Zhou, Y. C. (2008). A novel RNA-splicing mutation in COL1A1 gene causing osteogenesis imperfecta type I in a Chinese family. Clinica Chimica Acta; International Journal of Clinical Chemistry, 398(1-2), 148-51. https://doi.org/10.1016/j.cca.2008.07.030
Xia XY, et al. A Novel RNA-splicing Mutation in COL1A1 Gene Causing Osteogenesis Imperfecta Type I in a Chinese Family. Clin Chim Acta. 2008;398(1-2):148-51. PubMed PMID: 18755172.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel RNA-splicing mutation in COL1A1 gene causing osteogenesis imperfecta type I in a Chinese family. AU - Xia,Xin-Yi, AU - Cui,Ying-Xia, AU - Huang,Yu-Feng, AU - Pan,Lian-Jun, AU - Yang,Bin, AU - Wang,Hao-Yang, AU - Li,Xiao-Jun, AU - Shi,Yi-Chao, AU - Lu,Hong-Yong, AU - Zhou,Yu-Chun, Y1 - 2008/08/05/ PY - 2008/04/23/received PY - 2008/07/28/revised PY - 2008/07/31/accepted PY - 2008/8/30/pubmed PY - 2009/1/22/medline PY - 2008/8/30/entrez SP - 148 EP - 51 JF - Clinica chimica acta; international journal of clinical chemistry JO - Clin Chim Acta VL - 398 IS - 1-2 N2 - BACKGROUND: Osteogenesis imperfecta (OI), also known as brittle bone disease, is a rare heterogeneous group of inherited disorders characterized by low bone mass and increased bone fragility. The four major clinical criteria for diagnosis of OI are osteoporosis with abnormal fragility of the skeleton, blue sclera, dentinogenesis imperfecta, and premature otosclerosis. The presence of two of these abnormalities confirms the diagnosis. More than 90% patients have autosomal dominant mutations in one of the two genes, COL1A1 and COL1A2, that encode the alpha chains of type I collagen. While the diagnosis of OI is still based on clinical and radiological grounds, there is a growing demand for the molecular characterization of causative mutations. 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. The purpose of this study is to report two patients with OI type I in a Chinese family, who had a novel RNA-splicing mutation in COL1A1 gene and describe the molecular, radiological and clinical findings. METHODS: The proband, (case II-5), a 32-y-old Chinese male, and his 7-y-old daughter were diagnosed as OI type I according to their clinical and radiological features. Genomic DNA was extracted from their blood samples and all promoters, exons and exon/intron boundaries of COL1A1 and COL1A2 genes were sequenced. Polymerase chain reaction sequence-specific primers (PCR-SSP) was used to confirm patients' heterozygous state. RESULTS: Direct DNA sequencing analysis of COL1A1 gene revealed a splicing mutation (c.1875+1G>A, also as IVS 27+1G>A) that converted the 5' end of intron 27 from GT to AT. This mutation was found in both 2 affected individuals but 9 unaffected relatives and the 50 controls were not observed, which was consistent with the clinical diagnosis. This mutation (c.1875+1G>A) appeared to be novel, which is neither reported in literature nor registered in the Database of Collagen Mutations. The heterozygous states of patients' intron 27 were confirmed by PCR-SSP. CONCLUSION: We identify a novel RNA-splicing mutation (c.1875+1G>A) in COL1A1 gene resulting in OI type I in a Chinese family. The detailed molecular and clinical features will be useful for extending the evidence for genetic and phenotypic heterogeneity in OI and exploring the phenotype-genotype correlations in OI. SN - 0009-8981 UR - https://www.unboundmedicine.com/medline/citation/18755172/A_novel_RNA_splicing_mutation_in_COL1A1_gene_causing_osteogenesis_imperfecta_type_I_in_a_Chinese_family_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-8981(08)00385-9 DB - PRIME DP - Unbound Medicine ER -