Hereditary Pigmentary Disorders
Gene: DKC1
1 additional family reported with enterocolitis features.Created: 6 Jul 2023, 2:37 a.m. | Last Modified: 6 Jul 2023, 2:37 a.m.
Panel Version: 0.100
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
DKC1-related disorder - MONDO: 0100152
Publications
2 unrelated infants with infant-onset DKC - the most prominent clinical finding was the presence of a severe, chronic, non-infectious enteropathy leading to malabsorption and nutrient deficiencies . Histological abnormalities included inflammation and mucosal apoptosis (identical to gut GVHD) in the esophagus, small bowel, or colon. Phenotypic overlap with IBD. Review with Dr. Peter McNaughton (immunologist QCH).
Sources: Expert ReviewCreated: 23 Mar 2023, 11:55 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Dyskeratosis congenita
Publications
Variants in this GENE are reported as part of current diagnostic practice
Dyskeratosis congenita is classically defined by the triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa. It is characterized by short telomeres. Progressive bone marrow failure occurs in over 80% of cases and is the main cause of early mortality. The phenotype is highly variable, and affected individuals may have multiple additional features, including pulmonary fibrosis, liver cirrhosis, premature hair loss and/or graying, osteoporosis, atresia of the lacrimal ducts, and learning difficulties. Males may have testicular atrophy. Predisposition to malignancy is an important feature.
Hoyeraal-Hreidarsson syndrome (HHS) refers to a clinically severe variant of DKC that is characterized by multisystem involvement and early onset in utero. Patients with HHS show intrauterine growth retardation, microcephaly, delayed development, and bone marrow failure resulting in immunodeficiency, cerebellar hypoplasia, and sometimes enteropathy. Death often occurs in childhood.
PMID: 25940403, at least 13 of the variants associated with dyskeratosis congenita were also reported to cause HHS: P10L, I38T, T66A, T67I, H68Q, H68Y, S121G, R158W, K314R, A353V, R378Q, A386T and IVS12+1, so NOT only variants in exon 11. Two mutations were only found in HH, T49M and S304N.Created: 19 May 2021, 10:48 a.m. | Last Modified: 19 May 2021, 10:48 a.m.
Panel Version: 0.7643
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Dyskeratosis congenita, X-linked 305000; Hoyeraal-Hreidarsson Syndrome
Publications
Gene: dkc1 has been classified as Green List (High Evidence).
Gene: dkc1 has been classified as Green List (High Evidence).
gene: DKC1 was added gene: DKC1 was added to Hereditary Pigmentary Disorders. Sources: Expert list Mode of inheritance for gene: DKC1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: DKC1 were set to 31269755; 26951492; 29081935; 25940403 Phenotypes for gene: DKC1 were set to dyskeratosis congenita, X-linked MONDO:0010584