Tags

Type your tag names separated by a space and hit enter

[Screening and analysis of a new mutation of COL1A1 gene in a family with osteogenesis imperfecta].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2014 Jun; 31(3):344-7.ZY

Abstract

OBJECTIVE

To investigate mutation of COL1A1 gene and analyze the relationship between genotype and clinical phenotype in a family with osteogenesis imperfecta (OI).

METHODS

The family history of an OI pedigree, along with clinical data, was collected. Blood samples from the proband and his families, as well as 50 normal controls, were collected. Mutation of COL1A1 gene was screened using PCR-high resolution melting (PCR-HRM) and validated by sequencing.

RESULTS

PCR HRM method showed an abnormal result in proband COL1A133_34 exons, which Tm was 87.7℃, in contrast to the normal control (wt) Tm of 87.9±0.06℃. There was a significant difference between the proband and the normal control with the standardization curve and the difference curves. DNA sequencing showed that Y9COL1A1 gene exons 33_34 has lost a C base (c.2321delC), which resulted in a frameshift mutation and caused an premature termination codon (UAA) at amino acid 334, i.e., p.Pro774LeufsX334 The father and grandfather of the proband, both suffered from OI, were verified to be heterozygous for the same mutation. The same mutation was not found in 50 normal controls. Database search confirmed this to be a novel mutation. Pedigree analysis suggested that it has an autosomal dominant inheritance. The proband and patients from the family were clinically diagnosed as OI type I.

CONCLUSION

The study has identified a novel mutation of COL1A1 gene, c.2321delC. This frameshift mutation has caused a premature stop codon and reduced collagen type synthesis, characterized by a lighter OI clinical phenotype.

Authors+Show Affiliations

Department of Medical Laboratory, Tianjin Hospital, Tianjin 300211, P. R. China. Email: lig@tijmu.edu.cn.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

English Abstract
Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

24928016

Citation

Bai, Xue, et al. "[Screening and Analysis of a New Mutation of COL1A1 Gene in a Family With Osteogenesis Imperfecta]." Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics, vol. 31, no. 3, 2014, pp. 344-7.
Bai X, Li K, Ren X, et al. [Screening and analysis of a new mutation of COL1A1 gene in a family with osteogenesis imperfecta]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2014;31(3):344-7.
Bai, X., Li, K., Ren, X., He, X., Wang, Y., Guan, S., Jing, Y., & Li, G. (2014). [Screening and analysis of a new mutation of COL1A1 gene in a family with osteogenesis imperfecta]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics, 31(3), 344-7. https://doi.org/10.3760/cma.j.issn.1003-9406.2014.03.019
Bai X, et al. [Screening and Analysis of a New Mutation of COL1A1 Gene in a Family With Osteogenesis Imperfecta]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2014;31(3):344-7. PubMed PMID: 24928016.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Screening and analysis of a new mutation of COL1A1 gene in a family with osteogenesis imperfecta]. AU - Bai,Xue, AU - Li,Keqiu, AU - Ren,Xiuzhi, AU - He,Xiaobo, AU - Wang,Yi, AU - Guan,Shizhen, AU - Jing,Yaqing, AU - Li,Guang, PY - 2014/6/15/entrez PY - 2014/6/15/pubmed PY - 2014/7/30/medline SP - 344 EP - 7 JF - Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics JO - Zhonghua Yi Xue Yi Chuan Xue Za Zhi VL - 31 IS - 3 N2 - OBJECTIVE: To investigate mutation of COL1A1 gene and analyze the relationship between genotype and clinical phenotype in a family with osteogenesis imperfecta (OI). METHODS: The family history of an OI pedigree, along with clinical data, was collected. Blood samples from the proband and his families, as well as 50 normal controls, were collected. Mutation of COL1A1 gene was screened using PCR-high resolution melting (PCR-HRM) and validated by sequencing. RESULTS: PCR HRM method showed an abnormal result in proband COL1A133_34 exons, which Tm was 87.7℃, in contrast to the normal control (wt) Tm of 87.9±0.06℃. There was a significant difference between the proband and the normal control with the standardization curve and the difference curves. DNA sequencing showed that Y9COL1A1 gene exons 33_34 has lost a C base (c.2321delC), which resulted in a frameshift mutation and caused an premature termination codon (UAA) at amino acid 334, i.e., p.Pro774LeufsX334 The father and grandfather of the proband, both suffered from OI, were verified to be heterozygous for the same mutation. The same mutation was not found in 50 normal controls. Database search confirmed this to be a novel mutation. Pedigree analysis suggested that it has an autosomal dominant inheritance. The proband and patients from the family were clinically diagnosed as OI type I. CONCLUSION: The study has identified a novel mutation of COL1A1 gene, c.2321delC. This frameshift mutation has caused a premature stop codon and reduced collagen type synthesis, characterized by a lighter OI clinical phenotype. SN - 1003-9406 UR - https://www.unboundmedicine.com/medline/citation/24928016/[Screening_and_analysis_of_a_new_mutation_of_COL1A1_gene_in_a_family_with_osteogenesis_imperfecta]_ L2 - http://www.diseaseinfosearch.org/result/5451 DB - PRIME DP - Unbound Medicine ER -