Evidence of involvement of a novel VUS variant in the CHKB gene to congenital muscular dystrophy affection

Abstract

BackgroundCongenital muscular dystrophies (CMDs) are a group of clinical and genetic heterogeneous neuromuscular disorders with the onset of affection at birth or during infancy. Megaconial congenital muscular dystrophy (MDCMC) is a form of CMDs with the recessive inheritance. The CHKB gene on chromosome 22q13 is the responsible gene for this form of CMDs affection. Methods and resultsIn this study, a pedigree consisted of one affected member with clinical features involving mental retardation, myopathy, paresis and lack of speech was screened. The proband was showing abnormal myopathic and mental symptoms. By using the whole-exome sequencing method for genetic screening for the proband, we detected a homozygous variant in the CHKB gene, at position c.1129C > T (p.Arg377Trp); Chr22(GRCh37):g.51017669G > A. This is the first report of this variant in the scientific literature. This novel variant is classified as a variant with uncertain significance (class 3) according to the recommendations of ACMG. ConclusionThe mentioned variant in the CHKB gene is the candidate for the affected member's medical condition. The previously reported variations in the CHKB gene are also potentially related to the proband's medical condition. Moreover, In-silico analysis of the identified variant by MutationTaster, SIFT, PolyPhen-2, and PROVEAN software predicted that this variant is pathogenic and has damaging effects on the relevant protein function.