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ORIGINAL ARTICLE
Year : 2017  |  Volume : 1  |  Issue : 2  |  Page : 33-38

Whole exome sequencing analysis identifies a missense variant in COL1A2 gene which causes osteogenesis imperfecta Type IV in a family from Saudi Arabia


1 Department of Oral and Maxillofacial Prosthodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia
2 Centre for Human Genetics, Hazara University, Mansehra, Pakistan
3 Department of Molecular Science and Technology, Ajou University, Suwon, South Korea
4 Department of Zoology, Islamia College University, Peshawar, Pakistan
5 Centre for Human Genetics, Hazara University, Mansehra; Department of Zoology, Islamia College University, Peshawar, Pakistan
6 Princess Al-Jawhara Albrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia

Correspondence Address:
Musharraf Jelani
Princess Al-Jawhara Albrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah 21589
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jmsr.jmsr_26_17

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Objectives: Molecular diagnosis of a large Saudi family presenting an autosomal dominant form of osteogenesis imperfecta (OI). Methods: Genetic analysis of the index patient was performed through 100× paired end whole exome sequencing (WES) covering 24,000 coding genes of the human genome. The causative variant was filtered out among the previously known 23 genes' panel reported for 17 subtypes of OI. The dominant segregation of the causative variant with the disease phenotype was confirmed by Sanger sequencing. Pathogenicity of the altered protein was predicted through SIFT, PolyPhen, and MutationTaster software. Results: A heterozygous variant (c.1801G>A; p. Gly601Ser) in exon 31 of collagen 1α2 was identified. In this study, WES was successfully applied to identify the molecular basis of OI in the proband. The rest of family members were confirmed through Sanger validation confirming the autosomal dominant mode of inheritance in large Saudi family. Conclusion: OI is a rare heterogeneous disorder of connective tissues with 17 overlapping subtypes, for which 23 genes are known. Our work adds to the growing list of disease-causing variants in COL1A2. Reporting the disease-causing variants is one of the best ways to share data for better and accurate variants interpretation. We tested that WES can be used as an efficient tool for the molecular diagnosis of this rare phenotype.


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