ORPHA: 1775; DO: 0070017;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5q35.3 | Dyskeratosis congenita, autosomal recessive 2 | 613987 | Autosomal recessive | 3 | NHP2 | 606470 |
A number sign (#) is used with this entry because of evidence that autosomal recessive dyskeratosis congenita-2 (DKCB2) is caused by homozygous or compound heterozygous mutation in the NPH2 gene (606470) on chromosome 5q35.
Dyskeratosis congenita is a multisystem disorder caused by defective telomere maintenance. Clinical manifestations include mucocutaneous abnormalities, bone marrow failure, and an increased predisposition to cancer, among other variable features (summary by Vulliamy et al., 2008).
For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (127550).
Vulliamy et al. (2008) reported a Turkish man with nail dystrophy, thrombocytopenia, testicular atrophy, opportunistic infections, growth and mental retardation, liver cirrhosis, and intracranial calcification. His parents were asymptomatic and unrelated. An unrelated Turkish boy presented with dyskeratosis congenita at age 12 years. He had the classic mucocutaneous triad of nail dystrophy, leukoplakia, and reticulate skin pigmentation and developed peripheral pancytopenia due to progressive bone marrow failure. No other somatic abnormalities were reported. His parents were asymptomatic. Both patients had shortened telomeres and decreased levels of serum TERC (602322) RNA.
In 2 unrelated Turkish patients with autosomal recessive dyskeratosis congenita, Vulliamy et al. (2008) identified biallelic mutations in the NPH2 gene (606470.0001-606470.0003). The 2 patients were identified from a larger group of 117 patients with the disorder; no other pathogenic NPH2 variants and no mutations in the GAR1 gene (606468) were identified.
Vulliamy, T., Beswick, R., Kirwan, M., Marrone, A., Digweed, M., Walne, A., Dokal, I. Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita. Proc. Nat. Acad. Sci. 105: 8073-8078, 2008. [PubMed: 18523010] [Full Text: https://doi.org/10.1073/pnas.0800042105]