Identification of DKC1 Gene Novel Mutations in Patient with X-Linked Dyskeratosis Congenita

Abstract

Dyskeratosis congenita (DKC) is a rare inherited multisystem disorder characterized by the triad of abnormal skin pigmentation, nail dystrophy and mucosal leukoplakia. Bone marrow failure is the major cause of early mortality with additional predispositions to malignant disease and fatal pulmonary complications. The inheritance pattern is X-linked recessive in most cases, while autosomal dominant and autosomal recessive forms have also been documented. It is caused predominantly by missense mutations in the DKC1 gene mapped to chromosome Xq28. The dysfunction of DKC1 encoded protein, dyskerin, may lead to the destabilization and decreased activity of telomerase. We report a 10-year-old boy with typical features and diagnosed as X-linked DKC through gene analysis. The direct genomic sequencing of DKC1 gene showed a novel mutation of A to G in exon 11 nt 1,096 in both the proband and his mother. This missense mutation leads to a substitution from V to I at location 366.