Abstract:

To collect and analyze the clinical phenotypes and genotypes characteristics of two pediatric patients with Cockayne syndrome (CS). Peripheral blood was collected. Whole exome sequencing of a family of three was performed for the proband 1’s family, and targeted next-generation sequencing of the skin panel was carried out for proband 2 alone. Family verification of the variant sites was conducted by Sanger sequencing. Peripheral blood RNA of proband 1 was extracted, reverse-transcribed into cDNA, and then the splicing mutation was verified by Sanger sequencing. Proband 1 carried compound heterozygous mutations of ERCC5 (NM_000123.4) c.381-2A>G and c.403dup (T135NfsX28). Proband 2 carried a homozygous nonsense mutation of ERCC6 (NM_000124) c.643G>T (p.E215X). The mutations of c.381-2A>Gand c.403dup (T135NfsX28) in the ERCC5 gene have not been reported previously. The verification of the splicing mutation revealed that c.403dup was a homozygous mutant type. Therefore, it is speculated that the splicing mutation and the duplication mutation are not on the same haplotype. The splicing mutation affects splicing, and the generated mutant leads to the degradation of mRNA. For rare lethal and disabling diseases such as Cockayne syndrome, early diagnosis and early intervention should be carried out. The reports of genotypes and clinical phenotypes are crucial for guiding the prognosis.

Key words: Cockayne syndrome, ERCC5 gene, ERCC6 gene, photosensitive disease, hereditary dermatosis