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. 2017 Sep;21(5):338-41.
doi: 10.18869/acadpub.ibj.21.5.338. Epub 2017 Apr 22.

Next-Generation Sequencing Reveals One Novel Missense Mutation in COL1A2 Gene in an Iranian Family with Osteogenesis imperfecta

Farah Talebi  1 , Farideh Ghanbari Mardasi  1   2 , Mohammadi Asl Javad  3 , Bavarsad Amir Hooshang  4 , Salehi Kambo Masoumeh  2
Affiliations

Next-Generation Sequencing Reveals One Novel Missense Mutation in COL1A2 Gene in an Iranian Family with Osteogenesis imperfecta

Farah Talebi et al. Iran Biomed J. 2017 Sep.

Abstract

Background: Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous disorder characterized by bone loss and bone fragility. The aim of this study was to investigate the variants of three genes involved in the pathogenesis of OI.

Methods: Molecular genetic analyses were performed for COL1A1, COL1A2, and CRTAP genes in an Iranian family with OI. The DNA samples were analyzed by next-generation sequencing (NGS) gene panel and Sanger sequencing.

Results: Five different variants were identified in COL1A1 and COL1A2, including two variants in COL1A1 and three variants in COL1A2. Among the five causative COL1A1 and COL1A2 variants, one novel variants, c.1081 G>A, was found in COL1A2, which was identified in two siblings.

Conclusion: Our finding extends the variant spectrum of the COL1A2 gene and has important implications for genetic counseling of families. The NGS is a powerful molecular diagnostic strategy for OI, a heterogeneous disorder.

Keywords: Collagen type I; COL1A2; Mutation; Osteogenesis imperfecta; Next-generation sequencing.

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Conflict of interest statement

CONFLICT OF INTEREST. None declared.

Figures

Fig. 1
Fig. 1
The summary of data from Osteogenesis imperfecta (OI) patients in an affected family. (A) Pedigree of family with OI shows three affected individuals in consanguineous family. The patients are denoted in black, and the proband is indicated by arrow. (B) Electropherogram analysis. The partial sequences of COL1A2 in the patient show that heterozygous variant (c.1081 G>A) in COL1A2 cosegregate with the phenotype. Mutated nucleotide is marked with vertical line (black). (C) Conservation analysis. Protein alignment indicates the conservation of the amino acid sequence of COL1A2 G361S between species around the variant site. This novel variant occurs at an evolutionarily conserved residue marked with vertical line (red). (D) Schematic representation of the COL1A2 gene showing a novel variant described in patients with OI and showing in which exon this was found.
See this image and copyright information in PMC

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