This report describes dyskeratosis congenita, X-linked (DKCX), which is a subtype of dyskeratosis congenita; DKCX exhibits X-linked recessive inheritance. The human gene implicated in this disease is dyskerin pseudouridine synthase 1 (DKC1), which encodes a protein that functions in two distinct complexes. It has a role in ribosome biogenesis, as part of the complex that catalyzes pseudouridylation of rRNA, and is also a component of telomerase. There is a single fly ortholog, Nop60B, for which classical amorphic and loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Since Drosophila species maintain telomeres by a different mechanism (see https://www.ncbi.nlm.nih.gov/books/NBK6617/), experiments using Dmel\Nop60B do not address the telomerase component of DKC1 function or dyskeratosis congenita pathology.
The human DKC1 gene has not been introduced into flies.
Amorphic (null) mutations of Nop60B are lethal in the late embryonic stage; a hypomorphic mutation is male-sterile. Tissue-specific or localized reduction of Nop60B has been studied using UAS-RNAi constructs. A small number of genetic interactions and physical interaction(s) of Dmel\Nop60B have been described; see below and in the gene report for Nop60B.
[updated Jul. 2017 by FlyBase; FBrf0222196]
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 (summary by Kirwan and Dokal, 2008; pubmed:18005359). [from MIM:305000; 2016.11.07]
[DYSKERATOSIS CONGENITA, X-LINKED; DKCX](https://omim.org/entry/305000)
[DYSKERIN; DKC1](https://omim.org/entry/300126)
See general description of dyskeratosis congenita, above.
X-linked dyskeratosis congenita (DKCX) is caused by mutation in the dyskerin (DKC1) gene.
The protein encoded by DKC1 functions in two distinct complexes, playing an active role in telomerase stabilization and maintenance, and also acting as the catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of ribosomal RNA. [from Gene Cards, DKC1; 2016.11.08]
Dyskerin (dyskerin pseudouridine synthase 1) is a nucleolar protein present in small nucleolar ribonucleoprotein particles that modify specific uridine residues of ribosomal RNA by converting them to pseudouridine. Dyskerin is also a component of the telomerase complex (summary by Mochizuki et al., 2004; pubmed:15240872). [from MIM:300126; 2016.11.07]
One to one: 1 human to 1 Drosophila.
High-scoring ortholog of human DKC1 (1 Drosophila to 1 human; reciprocal best hit). Dmel\Nop60B shares 66% identity and 79% similarity with the human gene.
