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...

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Main Authors: Lidiia Zhytnik, Katre Maasalu, Andrey Pashenko, Sergey Khmyzov, Ene Reimann, Ele Prans, Sulev Kõks, Aare Märtson
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-08-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fgene.2019.00722/full
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spelling doaj-ace4db967b544e34bee4ab357fd037dc2020-11-24T23:52:09ZengFrontiers Media S.A.Frontiers in Genetics1664-80212019-08-011010.3389/fgene.2019.00722438530COL1A1/2 Pathogenic Variants and Phenotype Characteristics in Ukrainian Osteogenesis Imperfecta PatientsLidiia Zhytnik0Katre Maasalu1Katre Maasalu2Andrey Pashenko3Sergey Khmyzov4Ene Reimann5Ene Reimann6Ele Prans7Sulev Kõks8Aare Märtson9Aare Märtson10Department of Traumatology and Orthopedics, University of Tartu, Tartu, EstoniaDepartment of Traumatology and Orthopedics, University of Tartu, Tartu, EstoniaClinic of Traumatology and Orthopedics, Tartu University Hospital, Tartu, EstoniaDepartment of Pediatric Orthopedics, Sytenko Institute of Spine and Joint Pathology, AMS Ukraine, Kharkiv, UkraineDepartment of Pediatric Orthopedics, Sytenko Institute of Spine and Joint Pathology, AMS Ukraine, Kharkiv, UkraineCentre of Translational Medicine, University of Tartu, Tartu, EstoniaDepartment of Pathophysiology, University of Tartu, Tartu, EstoniaDepartment of Pathophysiology, University of Tartu, Tartu, EstoniaPerron Institute for Neurological and Translational Science, QEII Medical Centre, Nedlands, WA, AustraliaDepartment of Traumatology and Orthopedics, University of Tartu, Tartu, EstoniaClinic of Traumatology and Orthopedics, Tartu University Hospital, Tartu, EstoniaOsteogenesis 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.https://www.frontiersin.org/article/10.3389/fgene.2019.00722/fullosteogenesis imperfectacollagen ICOL1A1COL1A2Sanger sequencingbone disorder
collection DOAJ
language English
format Article
sources DOAJ
author Lidiia Zhytnik
Katre Maasalu
Katre Maasalu
Andrey Pashenko
Sergey Khmyzov
Ene Reimann
Ene Reimann
Ele Prans
Sulev Kõks
Aare Märtson
Aare Märtson
spellingShingle Lidiia Zhytnik
Katre Maasalu
Katre Maasalu
Andrey Pashenko
Sergey Khmyzov
Ene Reimann
Ene Reimann
Ele Prans
Sulev Kõks
Aare Märtson
Aare Märtson
COL1A1/2 Pathogenic Variants and Phenotype Characteristics in Ukrainian Osteogenesis Imperfecta Patients
Frontiers in Genetics
osteogenesis imperfecta
collagen I
COL1A1
COL1A2
Sanger sequencing
bone disorder
author_facet Lidiia Zhytnik
Katre Maasalu
Katre Maasalu
Andrey Pashenko
Sergey Khmyzov
Ene Reimann
Ene Reimann
Ele Prans
Sulev Kõks
Aare Märtson
Aare Märtson
author_sort Lidiia Zhytnik
title 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_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_sort col1a1/2 pathogenic variants and phenotype characteristics in ukrainian osteogenesis imperfecta patients
publisher Frontiers Media S.A.
series Frontiers in Genetics
issn 1664-8021
publishDate 2019-08-01
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.
topic osteogenesis imperfecta
collagen I
COL1A1
COL1A2
Sanger sequencing
bone disorder
url https://www.frontiersin.org/article/10.3389/fgene.2019.00722/full
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