DETECTION OF A NOVEL MUTATION IN THE PROTEOGLYCAN-4 GENE CAUSING CAMPTODACTYLY ARTHROPATHY COXA-VARA PERICARDITIS (CACP)

Abstract

Background: The Camptodactyly Arthropathy Coxa-Vara Pericarditis (CACP) syndrome is a rare autosomal recessive condition characterized by camptodactyly, non-inflammatory arthropathy, coxa-vara abnormality development, and pericarditis. This study investigates the molecular screening of CACP within autosomal recessive inheritance patterns. Methods: A large consanguineous family from Tehsil Domel district Bannu, Khyber Pakhtunkhwa province, Pakistan, was sampled. deoxy ribo nucleic Acid (DNA) extraction was performed on family subjects, followed by whole exome sequencing, Sanger sequencing and relevant online software analysis to identify the mutated gene. Additionally, computational analysis of mutated and unmutated protoglycane 4 (PRG4) gene structures was conducted to assess protein structure. Results: Investigation of whole exome sequencing data highlighted the role and expression of genes involved in limb deformities, joint inflammation, synovial malformation and cardiac abnormalities. Sanger sequencing revealed a homozygous frame shift 4 base pair (4-bp) deletion mutation (c.3007_3010delGAAA, p.Glu1003fs) in the PRG4 gene on chromosome 1q25eq31. Clinical features of family subjects included camptodactyly, osteoporosis, joint swelling and pain, synovial hyperplasia, and hip joint deformity without pericardial inflammation.. Conclusion: The present findings not only expands the variant spectrum of PRG4 but also be helpful in genetic counseling, prenatal diagnosis, and bringing awareness regarding the prevention of the disease among Pakistani population. Furthermore, the 3-dimensional models of the mutated and non mutated PRG4 was designed, refined and validated by computational analysis. The present study will reveal to avoid the cousin marriages and can lead to inherit the homozygous sequence variant state in the coming generations causing more sever clinical features.