Biallelic variants p.Arg1133Cys and p.Arg1379Cys in COL2A1:Further delineation of phenotypic spectrum of recessive Type 2 collagenopathies

Girisha, KM and Gandham, SriLakshmi Bhavani and Shah, Hitesh and Moirangthem, Amita and Shukla, Anju (2020) Biallelic variants p.Arg1133Cys and p.Arg1379Cys in COL2A1:Further delineation of phenotypic spectrum of recessive Type 2 collagenopathies. American Journal of Medical Genetics- Part A, 182. pp. 338-347. ISSN 1552-4825

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Abstract

The phenotypic spectrum of Type 2 collagenopathies ranges from lethal achondrogenesis Type 2 to milder osteoarthritis with mild chondrodysplasia. All of them are monoallelic except for the two recent reports showing that biallelic variants in COL2A1 can cause spondyloepiphyseal dysplasia congenita in two children. Here we report two additional families with homozygous variants, c.4135C>T (p.Arg1379Cys) and c.3190C>T (p.Arg1133Cys) in COL2A1 resulting in two distinct skeletal dysplasia phenotypes of intermediate severity. Though all six patients from four families exhibit a spondyloepimetaphyseal dysplasia, they demonstrate a wide variation in severity of short stature and involvement of epiphyses, metaphyses, and vertebrae. We hypothesize that the variants are likely to be hypomorphic, given the underlying mechanisms of disease causation for known heterozygous variants in COL2A1. With this report, we provide further evidence to the existence of autosomal recessive Type 2 collagenopathy

Item Type: Article
Uncontrolled Keywords: Autosomal recessive; Biallelic pathogenic variants; Exome sequencing; Short stature; Spondyloepi-metaphyseal dysplasia; Type 2 collagenopathies
Subjects: Medicine > KMC Manipal > Medicine
Medicine > KMC Manipal > Orthopaedics
Depositing User: KMC Library
Date Deposited: 14 Sep 2020 10:54
Last Modified: 14 Sep 2020 10:54
URI: http://eprints.manipal.edu/id/eprint/155590

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