Repot on a Second Case of Cockayne Syndrome in Zanjan Province due to a Missense Mutation in ERCC6 Gene

Background and Aim : Cockayne syndrome is a rare, autosomal-recessive disorder with a prevalence of approximately 2.5 per million, characterized by variety of clinical features including dwarfism, pigmentary retinopathy, cataracts, sensorineural deafness, ambulatory and feeding difficulties and premature pathological aging leading to death by 12 years of age. The signs and symptoms of this condition are usually apparent from infancy, and they worsen over time. Cockayne syndrome is associated with mutations in the genes CSA/ERCC8 or CSB/ERCC6, which have roles in DNA repair.Methods : Karyotype analysis was performed on peripheral blood lymphocytes. Also array comparative genomic hybridization (Array CGH) was done to check the gains and losses in the genome. Whole exome sequencing (WES) was performed using Agilent SureSelect V6 Target Enrichment Kit and the library was sequenced on Illumina Hiseq 4000 (Macrogen, South Korea). Nearly all exons and flanking 10bp were detected and analysed. Polymerase chain reaction (PCR) followed by sanger sequencing was used for confirm the detected mutation in patient and his parents.Results : The patient was an Iranian boy born of his consanguineous parents. The patient had severe neurological manifestations including microcephaly and cognitive deficits, impaired postnatal growth, intellectual disability, developmental delay and sensorineural hearing loss. His karyotype was normal. Array comparative genomic hybridization showed no abnormality. Whole exome sequencing revealed a homozygous missense variant in exon 13 (c.2551T> A; p.W851R) of ERCC6 gene in the patient. The parents and his sister were heterozygous for this mutation.Conclusion : We have used whole exome sequencing to identify a homozygous missense mutation in ERCC6 gene in an Iranian male patient with intellectual disability, developmental delay and dwarfism. Molecular findings were correlated with clinical outcome and confirmed the diagnosis of autosomal recessive Cockayne syndrome.

کلیدواژه ها:

Cockayne syndrome ، ERCC6 ، Whole exome sequencing