Background: Cockayne syndrome (CS) is a rare neurodegenerative disorder characterized by impaired neurological functions, cachectic dwarfism, microcephaly and photosensitivity. Complementation assays identify two groups of this disorder, CS type I (CSA) and CS type II (CSB), caused by mutations in ERCC8 and ERCC6, respectively.
Objectives: This study aimed to investigate the genetic basis of a consanguineous Pakistani family with three affected individuals presenting with typical clinical symptoms of CS.
Methods: We employed whole exome sequencing of the proband and then Sanger sequenced all the family members to confirm its segregation in the family. Different bioinformatics tools were used to predict pathogenicity of this variant.
Results: Variants were filtered according to the pedigree structure. We identified a novel homozygous variant (c.202A>T; p.Ile68Phe) in ERCC8 gene in the proband. The variant was found to segregate in the family.
Conclusions: These findings add to the genetic heterogeneity of ERCC8 and expands the mutation spectrum. Also, identification of this variant can facilitate prenatal diagnosis/genetic counselling set ups in Pakistan where this disease largely remains undiagnosed.
Keywords: CSA; Cockayne syndrome; ERCC8; WD40; photosensitivity.