Case Report: A Missense Mutation in Dyskeratosis Congenita 1 Leads to a Benign Form of Dyskeratosis Congenita Syndrome With the Mucocutaneous Triad

Abstract

BackgroundDyskeratosis congenita (DC) is a rare inheritable disorder characterized by bone marrow failure and mucocutaneous triad (reticular skin pigmentation, nail dystrophy, and oral leukoplakia). Dyskeratosis congenita 1 (DKC1) is responsible for 4.6% of the DC with an X-linked inheritance pattern. Almost 70 DKC1 variations causing DC have been reported in the Human Gene Mutation Database.ResultsHere we described a 14-year-old boy in a Chinese family with a phenotype of abnormal skin pigmentation on the neck, oral leukoplakia, and nail dysplasia in his hands and feet. Genetic analysis and sequencing revealed hemizygosity for a recurrent missense mutation c.1156G > A (p.Ala386Thr) in DKC1 gene. The heterozygous mutation (c.1156G > A) from his mother and wild-type sequence from his father were obtained in the same site of DKC1. This mutation was determined as disease causing based on silico software, but the pathological phenotypes of the proband were milder than previously reported at this position (HGMDCM060959). Homology modeling revealed that the altered amino acid was located near the PUA domain, which might affect the affinity for RNA binding.ConclusionThis DKC1 mutation (c.1156G > A, p.Ala386Thr) was first reported in a Chinese family with mucocutaneous triad phenotype. Our study reveals the pathogenesis of DKC1 c.1156G > A mutation to DC with a benign phenotype, which expands the disease variation database, the understanding of genotype–phenotype correlations, and facilitates the clinical diagnosis of DC in China.

Case report: A novel mutation in RTEL1 gene in dyskeratosis congenita

“…The disease is characterized by a variety of somatic abnormalities with some cases presenting with a classical triad of abnormal skin pigmentation, nail dystrophy, and mucosal leucoplakia (8)(9)(10)(11). Several genes have been linked to the pathophysiology of DKC including dyskeratosis congenita 1 (DKC1), CTS telomere maintenance complex component 1 (CTC1), regulator of telomere elongation helicase 1 (RTEL1), TERF 1-interacting nuclear factor 2 (TINF2), telomerase RNA component (TERC), telomerase reverse transcriptase (TERT), adrenocortical dysplasia homolog (ACD), NHP2 ribonucleoprotein (NHP2), NOP 10 ribonucleoprotein (NOP10), poly(A)-specific ribonuclease (PARN), nuclear assembly factor 1 (NAF1), and WD repeat containing antisense to TP53 (TCAB1) (12)(13)(14).…”