Tags

Type your tag names separated by a space and hit enter

Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta.
Eur J Hum Genet. 2015 Aug; 23(8):1042-50.EJ

Abstract

Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype-phenotype studies on >100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the α1- and α2-chains were associated with the absence of dentinogenesis imperfecta (P<0.0001 vs 0.0049), while only those in the α1-chain were associated with blue sclera (P=0.0110). Comparing glycine with serine substitutions, α1-alterations were associated with more severe phenotype (P=0.0031). Individuals with type I OI caused by qualitative vs quantitative mutations were shorter (P<0.0001), but did not differ considering fractures or BMD. The children in this cohort were estimated to represent >95% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in >95% of an entire OI population.

Authors+Show Affiliations

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.1] Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden [2] Neuropediatric Unit, Astrid Lindgren's Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.1] Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden [2] Department of Clinical Genetics, Karolinska University Hospital Stockholm, Stockholm, Sweden.1] Division of Pediatric Dentistry, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden [2] Division of Paediatrics, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital, Huddinge, Sweden.Department of Medical Sciences, Uppsala University, Uppsala, Sweden.1] Department of Medical Sciences, Uppsala University, Uppsala, Sweden [2] Science for Life Laboratory, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.

Pub Type(s)

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

Language

eng

PubMed ID

25944380

Citation

Lindahl, Katarina, et al. "Genetic Epidemiology, Prevalence, and Genotype-phenotype Correlations in the Swedish Population With Osteogenesis Imperfecta." European Journal of Human Genetics : EJHG, vol. 23, no. 8, 2015, pp. 1042-50.
Lindahl K, Åström E, Rubin CJ, et al. Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta. Eur J Hum Genet. 2015;23(8):1042-50.
Lindahl, K., Åström, E., Rubin, C. J., Grigelioniene, G., Malmgren, B., Ljunggren, Ö., & Kindmark, A. (2015). Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta. European Journal of Human Genetics : EJHG, 23(8), 1042-50. https://doi.org/10.1038/ejhg.2015.81
Lindahl K, et al. Genetic Epidemiology, Prevalence, and Genotype-phenotype Correlations in the Swedish Population With Osteogenesis Imperfecta. Eur J Hum Genet. 2015;23(8):1042-50. PubMed PMID: 25944380.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta. AU - Lindahl,Katarina, AU - Åström,Eva, AU - Rubin,Carl-Johan, AU - Grigelioniene,Giedre, AU - Malmgren,Barbro, AU - Ljunggren,Östen, AU - Kindmark,Andreas, Y1 - 2015/05/06/ PY - 2014/12/10/received PY - 2015/03/17/revised PY - 2015/03/20/accepted PY - 2015/5/7/entrez PY - 2015/5/7/pubmed PY - 2016/4/29/medline SP - 1042 EP - 50 JF - European journal of human genetics : EJHG JO - Eur J Hum Genet VL - 23 IS - 8 N2 - Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype-phenotype studies on >100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the α1- and α2-chains were associated with the absence of dentinogenesis imperfecta (P<0.0001 vs 0.0049), while only those in the α1-chain were associated with blue sclera (P=0.0110). Comparing glycine with serine substitutions, α1-alterations were associated with more severe phenotype (P=0.0031). Individuals with type I OI caused by qualitative vs quantitative mutations were shorter (P<0.0001), but did not differ considering fractures or BMD. The children in this cohort were estimated to represent >95% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in >95% of an entire OI population. SN - 1476-5438 UR - https://www.unboundmedicine.com/medline/citation/25944380/Genetic_epidemiology_prevalence_and_genotype_phenotype_correlations_in_the_Swedish_population_with_osteogenesis_imperfecta_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25944380/ DB - PRIME DP - Unbound Medicine ER -