Prenatal diagnosis identifies compound heterozygous variants in PKDCC that causes Rhizomelic Limb Shortening with Dysmorphic Features in a Chinese fetus

Abstract

Background: Rhizomelic limb shortening with dysmorphic features (RLSDF) has already been a disorder of the rare autosomal recessive skeletal dysplasia, just having a few reported cases. RLSDF is caused by PKDCC gene variants. In this article, the clinical features and potential RLSDF molecular etiology in a Chinese fetus are depicted. Methods: Genomic DNA (gDNA) extracted from the fetal muscle tissue and parents’ peripheral blood was subjected to chromosomal microarray analysis (CMA) and trio-based whole exome sequencing (Trio-WES). The candidate pathogenic variants were verified by Sanger sequencing. Results: Trio-WES identifed two compound heterozygous variants in PKDCC, c.346delC (p.Pro117Argfs*113) and c.994G>T (p.Glu332Ter), inherited from the father and mother, respectively. Both variants are classified as pathogenic according to ACMG guidelines. Conclusions: It was reported the first prenatal case of PKDCC caused RLSDF among Chinese population. Our findings extended the variation spectrum of PKDCC and emphasized the necessity of WES for early diagnosis of fetuses with skeletal dysplasia and other ultrasound structural abnormalities.