dyskeratosis congenita
Dyskeratosis congenita (DC) is a rare inherited syndrome characterized by the triad of abnormal skin pigmentation, nail dystrophy, mucosal leucoplakia and bone marrow failure syndrome.
Synopsis
aplastic anemia
bone marrow hypoplasia with bone marrow failure and pancytopenia (40%)
- anemia
- leucopenia
- thrombopenia
erythrokeratodermia variablis
chronic keratoconjunctivitis
nail dystrophy
esophageal lesions
- esophageal stenosis
Associations
idiopathic pulmonary fibrosis (usual interstitial pneumonia - UIP) (11641517, 9701856)
noncirrhotic portal hypertension (12925870)
squamous cell carcinoma
leukoplakia
gastric adenocarcinoma
Hodgkin?s disease (9729062)
Etiology
There are X-linked, autosomal dominant and autosomal recessive forms of the disease.
The X-linked form is due to mutations in the DKC1 gene at Xq28. The encoded protein, dyskerin, is a component of both small nucleolar ribonuclear protein particles and the telomerase complex. Mutations in DKC1 mainly lead to amino acid substitutions. (9590285)
The autosomal dominant form of the disease is due to mutations in hTR, the RNA component of telomerase (TERC), making it likely that the disease is due to defective telomerase activity. Mutations in hTR are predicted to either disrupt secondary structure or alter the template region.
recessive forms: no genes known (2003)
Reviews
Marrone A, Walne A, Dokal I. Dyskeratosis congenita: telomerase, telomeres and anticipation. Curr Opin Genet Dev. 2005 Jun;15(3):249-57. PMID: 15917199
Mason PJ, Wilson DB, Bessler M. Dyskeratosis congenita ? a disease of dysfunctional telomere maintenance. Curr Mol Med. 2005 Mar;5(2):159-70. PMID: 15974869
Bessler M, Wilson DB, Mason PJ. Dyskeratosis congenita and telomerase. Curr Opin Pediatr. 2004 Feb;16(1):23-8. PMID: 14758110
Marrone A, Mason PJ. Dyskeratosis congenita. Cell Mol Life Sci. 2003 Mar;60(3):507-17. PMID: 12737310
Meier UT. Dissecting dyskeratosis. Nat Genet. 2003 Feb;33(2):116-7. PMID: 12560816
Mason PJ. Stem cells, telomerase and dyskeratosis congenita. Bioessays. 2003 Feb;25(2):126-33. PMID: 12539238
Marciniak RA, Johnson FB, Guarente L. Dyskeratosis congenita, telomeres and human ageing. Trends Genet. 2000 May;16(5):193-5. PMID: 10782108
References
Amarasinghe K, Dalley C, Dokal I, Laurie A, Gupta V, Marsh J. Late death after unrelated-BMT for dyskeratosis congenita following conditioning with alemtuzumab, fludarabine and melphalan. Bone Marrow Transplant. 2007 Nov;40(9):913-4. PMID: 17724438
Brazzola P, Duval M, Fournet JC, Gauvin F, Dalle JH, Champagne J, Champagne MA. Fatal diffuse capillaritis after hematopoietic stem-cell transplantation for dyskeratosis congenita despite low-intensity conditioning regimen. Bone Marrow Transplant. 2005 Dec;36(12):1103-5; PMID: 16205731