COFS type 3 in an Indian family with antenatally detected arthrogryposis

Area of Science:

• Genetics
• Molecular Biology
• Developmental Biology

Background:

• Fetal akinesia and contractures present with diverse phenotypes, often linked to genetic mutations affecting DNA repair pathways.
• Cerebro-oculo-facio-skeletal (COFS) syndrome, a severe developmental disorder, involves genes like ERCC1, ERCC2, ERCC5, and ERCC6, crucial for DNA repair.
• ERCC5 gene mutations are primarily associated with xeroderma pigmentosum and occasionally with COFS syndrome.

Observation:

• A case report details a neonate with antenatally diagnosed arthrogryposis.
• Targeted next-generation sequencing identified a homozygous pathogenic variant in exon 8 of the ERCC5 gene.
• This variant is predicted to result in premature protein chain termination.

Findings:

• The identified homozygous ERCC5 variant is a novel cause of severe fetal akinesia and contractures.
• The mutation disrupts the DNA repair function of the ERCC5 protein, contributing to the observed phenotype.
• This finding expands the genotypic spectrum associated with ERCC5-related disorders.

Implications:

• This case highlights the importance of ERCC5 in fetal development and DNA repair.
• Understanding ERCC5 variants aids in diagnosing complex congenital anomalies and genetic counseling.
• Further research into ERCC5 function can elucidate mechanisms underlying developmental disorders and DNA repair deficiencies.