Two Novel Heterozygous Mutations in ERCC8 Cause Cockayne Syndrome in a Chinese Patient

摘要

BACKGROUND: Cockayne syndrome (MIM #133540, Cockayne syndrome B; 216400, Cockayne syndrome A) is a rare autosomal recessive inherited disease in which the characteristic symptoms are premature aging, cachectic dwarfism, lack of subcutaneous fat, neurological alterations, light sensitivity, and failure to thrive. The mutated gene responsible for this syndrome has been identified as usually either CSA (CKN1, ERCC8) or CSB (ERCC6). In this study, we describe the case of a 7-year-old Chinese boy with characteristic symptoms of Cockayne syndrome A and the conduction of mutation screening of the CSA gene. METHODS: The patient was diagnosed with Cockayne syndrome in the pediatrics clinic for growth failure and developmental delay. We collected peripheral blood samples of the patient and his parents and then extracted the genomic DNA. DNA samples from control subjects and the patient were subjected to polymerase chain reaction amplification. All exons and the flanking intron-exon boundaries of CSA were amplified; then, the polymerase chain reaction products were directly sequenced for mutation screening. RESULTS: Two novel heterozygous CSA mutations, c.551-2A>C and c.394_398delTTACA, were identified in the patient. The c.551-2A>C mutation originates from his father and changed the splice acceptor site AG to CG, thus possibly causing alternative splicing. The c.394_398deITTACA from his mother caused a frameshift after the amino acid at position 132, thus introducing a premature stop codon in the gene sequence. CONCLUSIONS: These mutations extend the mutation spectrum of Cockayne syndrome in the context of Chinese race and provide possibilities of prenatal diagnosis for future offsprings in this family.