Prenatal diagnosis to identify compound heterozygous variants in PKDCC that causes rhizomelic limb shortening with dysmorphic features in a fetus from China

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 protein kinase domain containing, cytoplasmic(PKDCC)gene variants. In this study, we describe the clinical features and potential RLSDF molecular etiology in a fetus from China. 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 using Sanger sequencing. Results Trio-WES identified 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 American College of Medical Genetics and Genomics guidelines. Conclusions We reported the first prenatal case of RLSDF caused by PKDCC in the Chinese population. Our findings extended the variation spectrum of PKDCC and emphasized the necessity of WES for the early diagnosis of skeletal dysplasia and other ultrasound structural abnormalities in fetuses.

Prenatal diagnosis of a skeletal disorder characterized by rhizomelic shortening of limbs caused by compound heterozygous variants in the PKDCC gene: Case report and literature review

“…In 2023, Yan et al. ( 2023 ) reported the first prenatal case with rhizomelic limb shortening and dysmorphic features caused by compound heterozygous variants of the PKDCC gene, namely, c.346delC(p. Pro117Argfs*113) and c.994G>T(p.Glu332Ter), and neither variant was reported previously. In this case, the dysmorphic features were apparent with rhizomelic shortening of the upper limbs, prominent forehead, and nasal planus.…”

“…The detection rate for prenatal diagnosis of the skeletal disorder is 30%. From a literature review on the PubMed database, there are few reports of prenatal diagnosis on the PKDCC gene causing fetal skeletal dysplasia (Yan et al., 2023 ). In this study, we investigated the potential genetic cause of a fetus with rhizomelic shortening of limbs at 19 weeks of gestation using a sequential detection approach involving karyotyping, chromosome microarray analysis (CMA) and Trio‐total whole‐exome sequencing (Trio‐WES).…”