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

• Published in: Molecular genetics & genomic medicine Vol. 12; no. 6; pp. e2477 - n/a
• Main Authors: Wang, Jing, Yu, Huijun, Zhang, Xiaoying, Zhou, Xiuyun, Tan, Ya, Li, Zhi, Gu, Ying, Lin, Li
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.06.2024; John Wiley and Sons Inc; Wiley
• Subjects: Adult; Amniocentesis; Amniotic fluid; Bone dysplasia; Case reports; Chondrocytes; Clinical Report; Clinical Reports; Diagnosis; DNA microarrays; Female; Femur; Fetuses; Genes; Genetic counseling; Genetic testing; Genomes; Genomic analysis; Genomics; Gestation; Gestational age; Heterozygote; Humans; Humerus; Kinases; Limb Deformities, Congenital - diagnosis; Limb Deformities, Congenital - genetics; Limb Deformities, Congenital - pathology; Limbs; Literature reviews; Menstruation; Mineralization; Mutation; PKDCC gene; Pregnancy; Prenatal Diagnosis; Proteins; skeletal dysplasia; Skeleton; Software packages; Ultrasonic imaging; Whole genome sequencing; prenatal diagnosis; PKDCC gene; skeletal dysplasia
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.2477

Background The protein kinase domain containing cytoplasmic (PKDCC) gene (OMIM#618821) is associated with bone development. Biallelic variants in the PKDCC gene can cause rhizomelic limb shortening with dysmorphic features. Case Report A fetus was found to be rhizomelic limb shortening at 16 weeks of gestation and amniocentesis was performed at 19 weeks of gestation. Genomic DNA extracted from the amniotic fluid was subjected to chromosomal microarray analysis (CMA), and Trio‐total whole‐exome sequencing (Trio‐WES). Sanger sequencing was used to verify the candidate pathogenic variants. CMA was normal, while Trio‐WES identified two compound heterozygous variants in the PKDCC gene, namely c.417_c.423delCGGCGCG insTCATGGGCTCAGTACAC(p.G140fs*35) and c.345G>A (p.W115*,379). Then the fetus was aborted and the development of its bone cells were compared with that of a normal fetus of similar gestational age by histopathological examination. Clinical findings of the fetus were shortening humerus and femur, synophrys, much hair on the side face, simian line on the right palm, etc. Histopathological examination showed that the affected fetus had increased proliferative chondrocytes, widened proliferative bands, and delayed bone mineralization. Conclusions We reported a prenatal case of rhizomelic shortening of limbs caused by compound heterozygous variants in the PKDCC gene, which emphasized the important role of Trio‐WES for diagnosis of skeletal dysplasia in fetuses. Novel compound heterozygous variants in the protein kinase domain containing cytoplasmic gene can cause fetal rhizomelic shortening of limbs.