This report describes intellectual disability, autosomal recessive 71, a subtype of autosomal recessive intellectual disability. The human gene implicated is ALKBH8, which encodes alkB homolog 8, tRNA methyltransferase. There is one high-scoring fly ortholog, Dmel\Alkbh8, the only Drosophila metabotropic glutamate receptor, for which multiple genetic reagents, including amorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
The human ALKBH8 gene has not been introduced into flies.
Flies bearing amorphic alleles of Dmel\Alkbh8 exhibit defects in associative learning and memory as assayed by suppression of the proboscis extension reflex. This phenotype can be ameliorated by treatment with the antioxidant N-Acetylcysteine amide (FBch0000715).
[updated Jan. 2025 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, AUTOSOMAL RECESSIVE 71; MRT71](https://omim.org/entry/618504)
[AlkB HOMOLOG 8, tRNA METHYLTRANSFERASE; ALKBH8](https://omim.org/entry/613306)
Patients from a small number of families have been characterized. All exhibit global developmental delay, with many also exhibiting seizures and/or dysmorphic features. [from MIM:618504; 2025.01.28]
Autosomal recessive intellectual developmental disorder-71 (MRT71) is caused by homozygous mutation in the ALKBH8 gene on chromosome 11q22. [from MIM:618504; 2025.01.28]
AlkB proteins belong to a conserved family of nonheme, iron-dependent dioxygenases. ALKBH8 is unique among AlkB family proteins in that it contains an N-terminal RNA recognition motif (RRM) and a C-terminal S-adenosyl-L-methionine (SAM)-dependent methyltransferase (MT) motif in addition to the central conserved AlkB oxygenase domain (Fu et al., 2010; pubmed:20308323). [from MIM:613306; 2025.01.28]
One to one (1 human to 1 Drosophila); ALKBH8 has one high-scoring Drosophila ortholog, Alkbh8.
High-scoring ortholog of human ALKBH8 (1 Drosophila to 1 human).
