Premium
Biallelic variants p.Arg1133Cys and p.Arg1379Cys in COL2A1 : Further delineation of phenotypic spectrum of recessive Type 2 collagenopathies
Author(s) -
Girisha Katta M.,
Bhavani Gandham S.,
Shah Hitesh,
Moirangthem Amita,
Shukla Anju,
Kim OkHwa,
Nishimura Gen,
Mortier Geert R.
Publication year - 2020
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61414
Subject(s) - phenotype , genetics , osteochondrodysplasia , short stature , biology , dysplasia , genotype , gene , anatomy , endocrinology
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 spondylo‐epimetaphyseal 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.