Exome sequencing identified pathogenic variations in genetic forms of skeletal disorders

INTRODUCTION: Genetic disorders that related to the skeletal system are contributed to the disturbances in the complex processes of skeletal development, growth and homeostasis. The symptoms and etiologies of genetic forms of skeletal disorders are very heterogeneous, so it complicates the differential diagnosis of such diseases. Nowadays, whole-exome sequencing (WES) provides the ability of rapid and cost-effective molecular diagnosis of inherited disease.METHODS: 17cases represented the hallmark symptoms of skeletal disorder referred to Narges Genetics Diagnostic Laboratory from 2014 to 2018. The history and physical condition of the patients considered and they subjected to the whole-exome sequencing. The obtained genetic profile analyzed by bioinformatics tools. The candidate variants determined and then their validation and allele segregation confirmed by Sanger sequencing.RESULT: 4 cases diagnosed as Osteogenesis imperfect of which FKBP10, COL1A1 and COL1A2 were the causative genes in 3 cases, 1 case remained unknown. In 2 cases the CHST3 gene revealed as mutated gene that is responsible for Spondyloepiphyseal dysplasia with congenital joint dislocations syndrome. Mutations in NEK1 gene cause Short-rib thoracic dysplasia 6 with or without polydactylysyndrome that found in 2 patients. The other genes including BHLHA9, CYP27B1, PCNT, GPX4, and PYCR1 were responsible respectively for Camptosynpolydactyly, complex/Syndactyly, mesoaxialsynostotic with phalangeal reduction, Vitamin D-dependent rickets, type I, Microcephalicosteodysplastic primordial dwarfism, Spondylometaphyseal dysplasia, Sedaghatian type and Cutis laxa, autosomal recessive, type IIB found among patients. The genetic cause of 4 cases remained unknown.CONCLUSION: WES can be used to confirm the diagnosis of the genetic disorders. In complicated conditions which there are overlapping presentations while other molecular testing is time and cost consuming, WES is the most helpful strategy.

کلیدواژه ها:

exome sequencing ، skeletal disorders ،