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Genotype-phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I.
Eur J Hum Genet. 2010 Jun; 18(6):642-7.EJ

Abstract

Osteogenesis imperfecta (OI) is a heritable disorder with bone fragility that is often associated with short stature, tooth abnormalities (dentinogenesis imperfecta), and blue sclera. The most common mutations associated with OI result from the substitution for glycine by another amino acid in the triple helical domain of either the alpha1 or the alpha2 chain of collagen type I. In this study, we compared the results of genotype analysis and clinical examination in 161 OI patients (median age: 13 years) who had glycine mutations in the triple helical domain of alpha1(I) (n=67) or alpha2(I) (n=94). Serine substitutions were the most frequently encountered type of mutation in both chains. Compared with patients with serine substitutions in alpha2(I) (n=40), patients with serine substitutions in alpha1(I) (n=42) on average were shorter (median height z-score -6.0 vs -3.4; P=0.005), indicating that alpha1(I) mutations cause a more severe phenotype. Height correlated with the location of the mutation in the alpha2(I) chain but not in the alpha1(I) chain. Patients with mutations affecting the first 120 amino acids at the amino-terminal end of the collagen type I triple helix had blue sclera but did not have dentinogenesis imperfecta. Among patients from different families sharing the same mutation, about 90 and 75% were concordant for dentinogenesis imperfecta and blue sclera, respectively. These data should be useful to predict disease phenotype in newly diagnosed OI patients.

Authors+Show Affiliations

Genetics Unit, Shriners Hospital for Children, Montreal, QC, Canada. frauch@shriners.mcgill.caNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20087402

Citation

Rauch, Frank, et al. "Genotype-phenotype Correlations in Nonlethal Osteogenesis Imperfecta Caused By Mutations in the Helical Domain of Collagen Type I." European Journal of Human Genetics : EJHG, vol. 18, no. 6, 2010, pp. 642-7.
Rauch F, Lalic L, Roughley P, et al. Genotype-phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I. Eur J Hum Genet. 2010;18(6):642-7.
Rauch, F., Lalic, L., Roughley, P., & Glorieux, F. H. (2010). Genotype-phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I. European Journal of Human Genetics : EJHG, 18(6), 642-7. https://doi.org/10.1038/ejhg.2009.242
Rauch F, et al. Genotype-phenotype Correlations in Nonlethal Osteogenesis Imperfecta Caused By Mutations in the Helical Domain of Collagen Type I. Eur J Hum Genet. 2010;18(6):642-7. PubMed PMID: 20087402.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genotype-phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I. AU - Rauch,Frank, AU - Lalic,Liljana, AU - Roughley,Peter, AU - Glorieux,Francis H, Y1 - 2010/01/20/ PY - 2010/1/21/entrez PY - 2010/1/21/pubmed PY - 2010/9/9/medline SP - 642 EP - 7 JF - European journal of human genetics : EJHG JO - Eur J Hum Genet VL - 18 IS - 6 N2 - Osteogenesis imperfecta (OI) is a heritable disorder with bone fragility that is often associated with short stature, tooth abnormalities (dentinogenesis imperfecta), and blue sclera. The most common mutations associated with OI result from the substitution for glycine by another amino acid in the triple helical domain of either the alpha1 or the alpha2 chain of collagen type I. In this study, we compared the results of genotype analysis and clinical examination in 161 OI patients (median age: 13 years) who had glycine mutations in the triple helical domain of alpha1(I) (n=67) or alpha2(I) (n=94). Serine substitutions were the most frequently encountered type of mutation in both chains. Compared with patients with serine substitutions in alpha2(I) (n=40), patients with serine substitutions in alpha1(I) (n=42) on average were shorter (median height z-score -6.0 vs -3.4; P=0.005), indicating that alpha1(I) mutations cause a more severe phenotype. Height correlated with the location of the mutation in the alpha2(I) chain but not in the alpha1(I) chain. Patients with mutations affecting the first 120 amino acids at the amino-terminal end of the collagen type I triple helix had blue sclera but did not have dentinogenesis imperfecta. Among patients from different families sharing the same mutation, about 90 and 75% were concordant for dentinogenesis imperfecta and blue sclera, respectively. These data should be useful to predict disease phenotype in newly diagnosed OI patients. SN - 1476-5438 UR - https://www.unboundmedicine.com/medline/citation/20087402/Genotype_phenotype_correlations_in_nonlethal_osteogenesis_imperfecta_caused_by_mutations_in_the_helical_domain_of_collagen_type_I_ L2 - https://doi.org/10.1038/ejhg.2009.242 DB - PRIME DP - Unbound Medicine ER -