Dyskeratosis congenita is a multisystem disorder caused by defective telomere maintenance. Features are variable and include bone marrow failure, pulmonary and liver fibrosis, and premature graying of the hair (summary by Armanios et al., 2005).
For ... Dyskeratosis congenita is a multisystem disorder caused by defective telomere maintenance. Features are variable and include bone marrow failure, pulmonary and liver fibrosis, and premature graying of the hair (summary by Armanios et al., 2005). For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (127550).
Armanios et al. (2005) reported a 3-generation family in which at least 6 members had autosomal dominant dyskeratosis congenita without skin manifestations. Common but variable features included gray forelock or premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary ... Armanios et al. (2005) reported a 3-generation family in which at least 6 members had autosomal dominant dyskeratosis congenita without skin manifestations. Common but variable features included gray forelock or premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, liver fibrosis, and abnormal dentition. Anticipation of clinical features was observed, and all affected individuals showed increased frequency of short telomeres compared to unaffected family members. Molecular analysis excluded the TERC gene (602322) and identified a pathogenic heterozygous mutation in the TERT gene (187270.0007). Basel-Vanagaite et al. (2008) reported an Iraqi Jewish family with autosomal dominant dyskeratosis congenita-2. Affected males presented with thrombocytopenia, and later developed aplastic anemia, premature graying of the hair, and pulmonary and hepatic fibrosis. One patient developed cardiac fibrosis and another developed dilated cardiomyopathy. Anticipation for these features was observed. Whereas all 6 males of the family were severely affected, 2 female mutation carriers had only premature gray hair; however, all mutation carriers had a similar shortening of telomere length. - Autosomal Recessive Dyskeratosis Congenita-4 Marrone et al. (2007) reported 2 unrelated patients, both born of consanguineous parents, with autosomal recessive dyskeratosis congenita-4. A 13-year-old Libyan girl had poor growth, bone marrow failure, reticulated pigmentation of the skin, leukoplakia, and nail dysplasia. Her parents had mild manifestations, such as dysplastic toenails and hyperpigmented skin. The second patient was a 3-year-old girl, born of consanguineous Iranian-Jewish parents, who had early bone marrow failure, leukoplakia, failure to thrive, cerebellar hypoplasia, microcephaly, and developmental delay. Telomere lengths were severely shortened in the patient and at the low-normal level in each parent. Marrone et al. (2007) noted that the presence of developmental delay and cerebellar hypoplasia in the second patient was consistent with a clinical diagnosis of Hoyeraal-Hreidarsson syndrome, which is a severe variant of DKC. Du et al. (2008) reported a 31-year-old Scottish man with DKCB4 who had a severe phenotype, including short stature, elfin appearance, esophageal stricture, leukoplakia of the buccal mucosa, anus, and penis, abnormal pigmentation, hyperkeratosis of his palms, ridged fingernails, avascular necrosis of both hips, tooth loss, chronic diarrhea, learning difficulties, pulmonary infiltrates, and progressive bone marrow failure. Laboratory studies showed very short telomeres, and genetic analysis showed a homozygous mutation in the TERT gene (187270.0014).
In all 6 affected members of a family with autosomal dominant dyskeratosis congenita, Armanios et al. (2005) identified a heterozygous mutation in the TERT gene (K902N; 187270.0007).
In affected members of an Iraqi Jewish family with ... In all 6 affected members of a family with autosomal dominant dyskeratosis congenita, Armanios et al. (2005) identified a heterozygous mutation in the TERT gene (K902N; 187270.0007). In affected members of an Iraqi Jewish family with DKCA2, Basel-Vanagaite et al. (2008) identified a heterozygous mutation in the TERT gene (R631Q; 187270.0011). - Autosomal Recessive Dyskeratosis Congenita 4 Marrone et al. (2007) identified homozygous TERT mutations (187270.0012 and 187270.0013) in patients with a severe form of autosomal recessive dyskeratosis congenita-4.