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COL1A1/2 Pathogenic Variants and Phenotype Characteristics in Ukrainian Osteogenesis Imperfecta Patients
Osteogenesis imperfecta (OI) is a hereditary bone disorder caused by defects of type I collagen. Although up to 90% of patients harbor pathogenic variants in the COL1A1/2 gene, which codes for collagen α1/2 chains, the spectrum of OI genotypes may differ between populations, and there is academic co...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696896/ https://www.ncbi.nlm.nih.gov/pubmed/31447884 http://dx.doi.org/10.3389/fgene.2019.00722 |
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author | Zhytnik, Lidiia Maasalu, Katre Pashenko, Andrey Khmyzov, Sergey Reimann, Ene Prans, Ele Kõks, Sulev Märtson, Aare |
author_facet | Zhytnik, Lidiia Maasalu, Katre Pashenko, Andrey Khmyzov, Sergey Reimann, Ene Prans, Ele Kõks, Sulev Märtson, Aare |
author_sort | Zhytnik, Lidiia |
collection | PubMed |
description | Osteogenesis imperfecta (OI) is a hereditary bone disorder caused by defects of type I collagen. Although up to 90% of patients harbor pathogenic variants in the COL1A1/2 gene, which codes for collagen α1/2 chains, the spectrum of OI genotypes may differ between populations, and there is academic controversy around OI genotype-phenotype correlations. In the current study, 94 Ukrainian OI families were interviewed. Clinical and genealogical information was collected from patients in spoken form, and their phenotypes were described. To identify the spectrum of collagen I pathogenic variants, COL1A1/2 mutational analysis with Sanger sequencing was performed on the youngest affected individual of every family. Of the 143 patients investigated, 67 (46.85%) had type I OI, 24 (16.78%) had type III, 49 (34.27%) had type IV, and III (2.10%) had type V. The mean number of fractures suffered per patient per year was 1.32 ± 2.88 (type I 0.50 ± 0.43; type III 3.51 ± 6.18; type IV 1.44 ± 1.77; and type 5 0.77 ± 0.23). 87.23% of patients had skeletal deformations of different severity. Blue sclera, dentinogenesis imperfecta, and hearing loss were present in 87%, 55%, and 22% of patients, respectively. COL1A1/2 pathogenic variants were harbored by 60 patients (63.83%). 27 pathogenic variants are described herein for the first time. The majority of the pathogenic variants were located in the COL1A1 gene (76.19%). Half (49.21%) of the pathogenic variants were represented by structural variants. OI phenotype severity was highly correlated with type of collagen I defect. The current article presents an analysis of the clinical manifestations and COL1A1/2 mutational spectrum of 94 Ukrainian OI families with 27 novel COL1A1/2 pathogenic variants. It is hoped that this data and its analysis will contribute toward the increased understanding of the phenotype development and genetics of the disorder. |
format | Online Article Text |
id | pubmed-6696896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66968962019-08-23 COL1A1/2 Pathogenic Variants and Phenotype Characteristics in Ukrainian Osteogenesis Imperfecta Patients Zhytnik, Lidiia Maasalu, Katre Pashenko, Andrey Khmyzov, Sergey Reimann, Ene Prans, Ele Kõks, Sulev Märtson, Aare Front Genet Genetics Osteogenesis imperfecta (OI) is a hereditary bone disorder caused by defects of type I collagen. Although up to 90% of patients harbor pathogenic variants in the COL1A1/2 gene, which codes for collagen α1/2 chains, the spectrum of OI genotypes may differ between populations, and there is academic controversy around OI genotype-phenotype correlations. In the current study, 94 Ukrainian OI families were interviewed. Clinical and genealogical information was collected from patients in spoken form, and their phenotypes were described. To identify the spectrum of collagen I pathogenic variants, COL1A1/2 mutational analysis with Sanger sequencing was performed on the youngest affected individual of every family. Of the 143 patients investigated, 67 (46.85%) had type I OI, 24 (16.78%) had type III, 49 (34.27%) had type IV, and III (2.10%) had type V. The mean number of fractures suffered per patient per year was 1.32 ± 2.88 (type I 0.50 ± 0.43; type III 3.51 ± 6.18; type IV 1.44 ± 1.77; and type 5 0.77 ± 0.23). 87.23% of patients had skeletal deformations of different severity. Blue sclera, dentinogenesis imperfecta, and hearing loss were present in 87%, 55%, and 22% of patients, respectively. COL1A1/2 pathogenic variants were harbored by 60 patients (63.83%). 27 pathogenic variants are described herein for the first time. The majority of the pathogenic variants were located in the COL1A1 gene (76.19%). Half (49.21%) of the pathogenic variants were represented by structural variants. OI phenotype severity was highly correlated with type of collagen I defect. The current article presents an analysis of the clinical manifestations and COL1A1/2 mutational spectrum of 94 Ukrainian OI families with 27 novel COL1A1/2 pathogenic variants. It is hoped that this data and its analysis will contribute toward the increased understanding of the phenotype development and genetics of the disorder. Frontiers Media S.A. 2019-08-09 /pmc/articles/PMC6696896/ /pubmed/31447884 http://dx.doi.org/10.3389/fgene.2019.00722 Text en Copyright © 2019 Zhytnik, Maasalu, Pashenko, Khmyzov, Reimann, Prans, Kõks and Märtson http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Zhytnik, Lidiia Maasalu, Katre Pashenko, Andrey Khmyzov, Sergey Reimann, Ene Prans, Ele Kõks, Sulev Märtson, Aare COL1A1/2 Pathogenic Variants and Phenotype Characteristics in Ukrainian Osteogenesis Imperfecta Patients |
title |
COL1A1/2 Pathogenic Variants and Phenotype Characteristics in Ukrainian Osteogenesis Imperfecta Patients |
title_full |
COL1A1/2 Pathogenic Variants and Phenotype Characteristics in Ukrainian Osteogenesis Imperfecta Patients |
title_fullStr |
COL1A1/2 Pathogenic Variants and Phenotype Characteristics in Ukrainian Osteogenesis Imperfecta Patients |
title_full_unstemmed |
COL1A1/2 Pathogenic Variants and Phenotype Characteristics in Ukrainian Osteogenesis Imperfecta Patients |
title_short |
COL1A1/2 Pathogenic Variants and Phenotype Characteristics in Ukrainian Osteogenesis Imperfecta Patients |
title_sort | col1a1/2 pathogenic variants and phenotype characteristics in ukrainian osteogenesis imperfecta patients |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696896/ https://www.ncbi.nlm.nih.gov/pubmed/31447884 http://dx.doi.org/10.3389/fgene.2019.00722 |
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