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Genotype-phenotype correlation study in 364 osteogenesis imperfecta Italian patients.
Eur J Hum Genet. 2019 07; 27(7):1090-1100.EJ

Abstract

Osteogenesis imperfecta (OI) is a rare genetic disorder of the connective tissue and 90% of cases are due to dominant mutations in COL1A1 and COL1A2 genes. To increase OI disease knowledge and contribute to patient follow-up management, a homogeneous Italian cohort of 364 subjects affected by OI types I-IV was evaluated. The study population was composed of 262 OI type I, 24 type II, 39 type III, and 39 type IV patients. Three hundred and nine subjects had a type I collagen affecting function mutations (230 in α1(I) and 79 in α2(I)); no disease-causing changes were noticed in 55 patients. Compared with previous genotype-phenotype OI correlation studies, additional observations arose: a new effect for α1- and α2-serine substitutions has been pointed out and heart defects, never considered before, resulted associated to quantitative mutations (P = 0.043). Moreover, some different findings emerged if compared with previous literature; especially, focusing the attention on the lethal form, no association with specific collagen regions was found and most of variants localized in the previously reported "lethal clusters" were causative of OI types I-IV. Some discrepancies have been highlighted also considering the "50-55 nucleotides rule," as well as the relationship between specific collagen I mutated region and the presence of dentinogenesis imperfecta and/or blue sclera. Despite difficulties still present in defining clear rules to predict the clinical outcome in OI patients, this study provides new pieces for completing the puzzle, also thanks to the inclusion of clinical signs never considered before and to the large number of OI Italian patients.

Authors+Show Affiliations

Department of Medical Genetics and Rare Orthopaedic Diseases, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. margherita.maioli@ior.it.Department of Medical Genetics and Rare Orthopaedic Diseases, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.CLIBI Laboratory, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.Department of Medical Genetics and Rare Orthopaedic Diseases, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.Department of Pediatrics, Center for Congenital Osteodystrophy - Sapienza University, Rome, Italy.Department of Medical Genetics and Rare Orthopaedic Diseases, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.CLIBI Laboratory, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.Department of Medical Genetics and Rare Orthopaedic Diseases, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.Department of Pediatrics, Center for Congenital Osteodystrophy - Sapienza University, Rome, Italy.Department of Pediatrics, Sapienza University, Rome, Italy.Department of Pediatrics, Center for Congenital Osteodystrophy - Sapienza University, Rome, Italy.Department of Medical Genetics and Rare Orthopaedic Diseases, and CLIBI Laboratory, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.

Pub Type(s)

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

Language

eng

PubMed ID

30886339

Citation

Maioli, Margherita, et al. "Genotype-phenotype Correlation Study in 364 Osteogenesis Imperfecta Italian Patients." European Journal of Human Genetics : EJHG, vol. 27, no. 7, 2019, pp. 1090-1100.
Maioli M, Gnoli M, Boarini M, et al. Genotype-phenotype correlation study in 364 osteogenesis imperfecta Italian patients. Eur J Hum Genet. 2019;27(7):1090-1100.
Maioli, M., Gnoli, M., Boarini, M., Tremosini, M., Zambrano, A., Pedrini, E., Mordenti, M., Corsini, S., D'Eufemia, P., Versacci, P., Celli, M., & Sangiorgi, L. (2019). Genotype-phenotype correlation study in 364 osteogenesis imperfecta Italian patients. European Journal of Human Genetics : EJHG, 27(7), 1090-1100. https://doi.org/10.1038/s41431-019-0373-x
Maioli M, et al. Genotype-phenotype Correlation Study in 364 Osteogenesis Imperfecta Italian Patients. Eur J Hum Genet. 2019;27(7):1090-1100. PubMed PMID: 30886339.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genotype-phenotype correlation study in 364 osteogenesis imperfecta Italian patients. AU - Maioli,Margherita, AU - Gnoli,Maria, AU - Boarini,Manila, AU - Tremosini,Morena, AU - Zambrano,Anna, AU - Pedrini,Elena, AU - Mordenti,Marina, AU - Corsini,Serena, AU - D'Eufemia,Patrizia, AU - Versacci,Paolo, AU - Celli,Mauro, AU - Sangiorgi,Luca, Y1 - 2019/03/18/ PY - 2018/05/04/received PY - 2019/02/26/accepted PY - 2019/02/06/revised PY - 2019/3/20/pubmed PY - 2020/6/12/medline PY - 2019/3/20/entrez SP - 1090 EP - 1100 JF - European journal of human genetics : EJHG JO - Eur J Hum Genet VL - 27 IS - 7 N2 - Osteogenesis imperfecta (OI) is a rare genetic disorder of the connective tissue and 90% of cases are due to dominant mutations in COL1A1 and COL1A2 genes. To increase OI disease knowledge and contribute to patient follow-up management, a homogeneous Italian cohort of 364 subjects affected by OI types I-IV was evaluated. The study population was composed of 262 OI type I, 24 type II, 39 type III, and 39 type IV patients. Three hundred and nine subjects had a type I collagen affecting function mutations (230 in α1(I) and 79 in α2(I)); no disease-causing changes were noticed in 55 patients. Compared with previous genotype-phenotype OI correlation studies, additional observations arose: a new effect for α1- and α2-serine substitutions has been pointed out and heart defects, never considered before, resulted associated to quantitative mutations (P = 0.043). Moreover, some different findings emerged if compared with previous literature; especially, focusing the attention on the lethal form, no association with specific collagen regions was found and most of variants localized in the previously reported "lethal clusters" were causative of OI types I-IV. Some discrepancies have been highlighted also considering the "50-55 nucleotides rule," as well as the relationship between specific collagen I mutated region and the presence of dentinogenesis imperfecta and/or blue sclera. Despite difficulties still present in defining clear rules to predict the clinical outcome in OI patients, this study provides new pieces for completing the puzzle, also thanks to the inclusion of clinical signs never considered before and to the large number of OI Italian patients. SN - 1476-5438 UR - https://www.unboundmedicine.com/medline/citation/30886339/Genotype_phenotype_correlation_study_in_364_osteogenesis_imperfecta_Italian_patients_ L2 - https://doi.org/10.1038/s41431-019-0373-x DB - PRIME DP - Unbound Medicine ER -