This report describes intellectual disability, X-linked, syndromic, Nascimento type; an alternative designation of this disease is 'mental retardation, X-linked, syndromic, Nascimento type' (MRXSH). MRXSN exhibits X-linked recessive inheritance. The human gene implicated in this disease is ubiquitin-conjugating enzyme E2A gene (UBE2A), which plays a role in epigenetic transcriptional regulation and is required for postreplication repair of UV-damaged DNA. There is a second similar gene in humans, UBE2B. There is a single Drosophila ortholog. Dmel\Ubc6, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
The human UBE2A gene has not been introduced into flies.
Loss-of-function mutations of Dmel\Ubc6 are lethal during larval or pupal stages. Phenotypes assessed during larval stages include defects in mitochondrial membrane potential in neuromuscular junctions and neurophysiology defects.
[updated Jun. 2017 by FlyBase; FBrf0222196]
Intellectual disability is characterized by impairments in intellectual functioning and adaptive behavior; symptoms must be present before a child becomes 18 years old (http://medical-dictionary.thefreedictionary.com/mental+retardation; 2016.01.19).
Intellectual disability can be subdivided into syndromic forms, characterized by cognitive impairment accompanied by dysmorphic features, malformations or neurological abnormalities, and nonsyndromic forms, characterized by cognitive impairment without additional features (Basel-Vanagaite, 2008; DOI: 10.1002/9780470015902.a0021454).
[INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, NASCIMENTO TYPE; MRXSN](https://omim.org/entry/300860)
[UBIQUITIN-CONJUGATING ENZYME E2 A; UBE2A](https://omim.org/entry/312180)
In addition to cognitive disability, males with the Nascimento type of X-linked syndromic mental retardation (MRXSN) exhibit characteristic dysmorphic features. Female carriers have normal cognition, but may show subtle facial features (summary by Budny et al., 2010; pubmed:20412111). [from MIM:300860; 2016.01.25]
MRXSN is caused by mutation in the ubiquitin-conjugating enzyme E2A gene (UBE2A); it is inherited as an X-linked recessive. [from MIM:300860; 2016.01.25] This gene is also known as RAD6A or HHR6A. [from MIM:312180; 2016.01.25]
UBE2A plays a role in post-translational control of multiple protein via its role in the protein ubiquitination pathway; specifically, it accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. A key target protein is histone 2B; ubiquitination of H2B plays a role in epigenetic transcription regulation. [from UniProt:P49459; 2016.01.25]
The UBE2A enzyme plays a role in epigenetic regulation of transcription by catalyzing the ubiquitination of histone H2B; it is required for postreplication repair of UV-damaged DNA. [Gene Cards, UBE2A; 2017.06.19]
Many to one: 2 human to 1 Drosophila. Two human genes, UBE2A and UBE2B, are orthologous to the fly gene Dmel\Ubc6.
Ortholog of human genes UBE2A and UBE2B (1 Drosophila to 2 human). Dmel\Ubc6 shares 86-88% identity and 93-94% similarity with the human genes and is almost identical in length.
