Tags

Type your tag names separated by a space and hit enter

Genetic and biochemical analyses of Israeli osteogenesis imperfecta patients.
Hum Mutat. 2004 Apr; 23(4):399-400.HM

Abstract

Osteogenesis imperfecta (OI) is clinically characterized by abnormal bone fragility, with most patients harboring heterozygote germline mutations in the COL1A1 or COL1A2 genes that encode the chains of type I procollagen, the major protein in bone. More than 250 mutations in both genes in OI patients have been reported, mostly missense mutations affecting glycine residues in the triple helical domains of the two chains. These mutations disrupt protein folding and structure, and their effects often can be detected by the analysis of proteins synthesized but cultured fibroblasts or, less often, osteoblasts. In this study, mutational analysis of all the COL1A1 and part of the COL1A2 was performed using exon-specific PCR amplification followed by denaturing gradient gel electrophoresis (DGGE) analysis and complemented by DNA sequencing in 57 Israeli OI patients from 55 unrelated families. Protein analysis was also performed using cultured fibroblasts obtained from a subset of these OI patients. Of 57 OI patients analyzed, 35 had OI type 1, 12 has OI type III, 8 had OI type IV, and 2 had OI type II. Fourteen different pathogenic mutations (10 novel) were identified in the COL1A1 gene: 3 missense, 5 nonsense, 3 insertion/deletion frameshift, 2 splice junction mutations, and 1 in frame deletion. We conclude that COL1A1 mutations underlie a subset of Israeli OI patients, that most commonly in OI type I, the mutations are contained within the COL1A1 gene, and that there are no predominant mutations in Jewish OI patients. Lastly, the use of protein analyses complements genetic analyses.

Authors+Show Affiliations

Sheba Medical Center, The Danek Gertner Institute of Genetics, Tel-Hashomer, Israel.No 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)

Journal Article

Language

eng

PubMed ID

15024745

Citation

Ries-Levavi, Liat, et al. "Genetic and Biochemical Analyses of Israeli Osteogenesis Imperfecta Patients." Human Mutation, vol. 23, no. 4, 2004, pp. 399-400.
Ries-Levavi L, Ish-Shalom T, Frydman M, et al. Genetic and biochemical analyses of Israeli osteogenesis imperfecta patients. Hum Mutat. 2004;23(4):399-400.
Ries-Levavi, L., Ish-Shalom, T., Frydman, M., Lev, D., Cohen, S., Barkai, G., Goldman, B., Byers, P., & Friedman, E. (2004). Genetic and biochemical analyses of Israeli osteogenesis imperfecta patients. Human Mutation, 23(4), 399-400.
Ries-Levavi L, et al. Genetic and Biochemical Analyses of Israeli Osteogenesis Imperfecta Patients. Hum Mutat. 2004;23(4):399-400. PubMed PMID: 15024745.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic and biochemical analyses of Israeli osteogenesis imperfecta patients. AU - Ries-Levavi,Liat, AU - Ish-Shalom,Tsofia, AU - Frydman,Moshe, AU - Lev,Dorit, AU - Cohen,Shirley, AU - Barkai,Gad, AU - Goldman,Boleslaw, AU - Byers,Peter, AU - Friedman,Eitan, PY - 2004/3/17/pubmed PY - 2004/5/7/medline PY - 2004/3/17/entrez SP - 399 EP - 400 JF - Human mutation JO - Hum Mutat VL - 23 IS - 4 N2 - Osteogenesis imperfecta (OI) is clinically characterized by abnormal bone fragility, with most patients harboring heterozygote germline mutations in the COL1A1 or COL1A2 genes that encode the chains of type I procollagen, the major protein in bone. More than 250 mutations in both genes in OI patients have been reported, mostly missense mutations affecting glycine residues in the triple helical domains of the two chains. These mutations disrupt protein folding and structure, and their effects often can be detected by the analysis of proteins synthesized but cultured fibroblasts or, less often, osteoblasts. In this study, mutational analysis of all the COL1A1 and part of the COL1A2 was performed using exon-specific PCR amplification followed by denaturing gradient gel electrophoresis (DGGE) analysis and complemented by DNA sequencing in 57 Israeli OI patients from 55 unrelated families. Protein analysis was also performed using cultured fibroblasts obtained from a subset of these OI patients. Of 57 OI patients analyzed, 35 had OI type 1, 12 has OI type III, 8 had OI type IV, and 2 had OI type II. Fourteen different pathogenic mutations (10 novel) were identified in the COL1A1 gene: 3 missense, 5 nonsense, 3 insertion/deletion frameshift, 2 splice junction mutations, and 1 in frame deletion. We conclude that COL1A1 mutations underlie a subset of Israeli OI patients, that most commonly in OI type I, the mutations are contained within the COL1A1 gene, and that there are no predominant mutations in Jewish OI patients. Lastly, the use of protein analyses complements genetic analyses. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/15024745/Genetic_and_biochemical_analyses_of_Israeli_osteogenesis_imperfecta_patients_ L2 - https://doi.org/10.1002/humu.9230 DB - PRIME DP - Unbound Medicine ER -