Open Close
General Information
Name
dyskeratosis congenita, X-linked
FlyBase ID
FBhh0000431
Disease Ontology Term
Parent Disease
Overview

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]

Disease Summary Information
Parent Disease Summary: dyskeratosis congenita
Symptoms and phenotype

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 OMIM:305000; 2016.11.07]

Specific Disease Summary: dyskeratosis congenita, X-linked
OMIM report

[DYSKERATOSIS CONGENITA, X-LINKED; DKCX](https://omim.org/entry/305000)

Human gene(s) implicated

[DYSKERIN; DKC1](https://omim.org/entry/300126)

Symptoms and phenotype

See general description of dyskeratosis congenita, above.

Genetics

X-linked dyskeratosis congenita (DKCX) is caused by mutation in the dyskerin (DKC1) gene.

Cellular phenotype and pathology
Molecular information

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 OMIM:300126; 2016.11.07]

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]

External links
Disease synonyms
DKCX
Zinsser-Cole-Engman syndrome
X-linked dyskeratosis
X-linked dyskeratosis congenita
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    One to one: 1 human to 1 Drosophila.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      Nucleolar protein at 60B (Nop60B) encodes a pseudouridine synthase that is a core component of H/ACA small nucleolar ribonucleoproteins (snoRNPs) and small Cajal body-specific ribonucleoproteins (scaRNPs). It is involved in pseudouridylation of cellular RNA, ribosome biogenesis, translation efficiency, cell proliferation, stress response and stem cell maintenance. [Date last reviewed: 2019-02-28]
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      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.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Synthetic Gene(s) Used (0)
      Summary of Physical Interactions (6 groups)
      protein-protein
      Interacting group
      Assay
      References
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry
      Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
      Models Based on Experimental Evidence ( 2 )
      Modifiers Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Interaction
      References
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Selected mammalian transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      amorphic allele - molecular evidence
      Delta2-3 transposase
      amorphic allele - molecular evidence
      Delta2-3 transposase
      amorphic allele - molecular evidence
      Delta2-3 transposase
      References (7)