Identification of a novel mutation and a de novo mutation in DKC1 in two Chinese pedigrees with dyskeratosis congenita

Abstract

Dyskeratosis congenita (DKC) is a rare and fatal congenital syndrome characterized by the triad of reticular skin pigmentation, nail dystrophy and mucosal leukoplakia, and the predisposition to bone marrow failure and malignancies. Mutations in DKC1 gene encoding dyskerin are responsible for the X-linked dyskeratosis congenita. Here we report mutation analysis of two Chinese pedigrees with dyskeratosis congenita. The 15 coding exons of DKC1 and their flanking regions were amplified from genomic DNA by PCR. DNA sequencing and restriction endonuclease digestion were used for mutation detection. Transition mutation of 1226C → T (P409L) found in the first pedigree is a novel mutation. In the second pedigree, the proband's mother phenotypically normal carried a de novo transition mutation of 1058C → T (A353V) in one allele, and transmitted the mutant allele to her two sons who had typical manifestations of dyskeratosis congenita.