This report describes a neurodevelopmental disorder with intellectual disability, autistic features, and language delay, with or without seizures (IDDALDS); IDDALDS exhibits autosomal dominant inheritance. The gene implicated in this disease is TANC2 (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2); TANC2 encodes a synaptic scaffolding protein that interacts with other proteins at the postsynaptic density to regulate dendritic spines and excitatory synapse formation. There is a single orthologous gene in Drosophila, rols, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated. Dmel\rols is also orthologous to the human gene TANC1.
A UAS construct of the wild-type human Hsap\TANC2 gene has been introduced into flies. Expression of the human gene fails to rescue the lethal phenotypes of a Dmel\rols loss-of-function mutation.
Animals homozygous for a loss-of-function allele of Dmel\rols typically die in the embryonic stage. In larvae and adults, rols is expressed predominantly in glia, with very little expression in neurons; expression in muscle is observed in early development, but very little in later stages. Expression of rols in the postsynapse is important for proper synaptic morphology and glutamate receptor clustering during the development of the neuromuscular junction (NMJ). Physical and genetic interactions of Dmel\rols have been described; see below and in the rols gene report.
[updated Jul. 2020 by FlyBase; FBrf0222196]
[INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISTIC FEATURES AND LANGUAGE DELAY, WITH OR WITHOUT SEIZURES; IDDALDS](https://omim.org/entry/618906)
[TETRATRICOPEPTIDE REPEAT-, ANKYRIN REPEAT-, AND COILED-COIL-CONTAINING PROTEIN 2; TANC2](https://omim.org/entry/615047)
Intellectual developmental disorder with autistic features and language delay, with or without seizures (IDDALDS), is a neurodevelopmental disorder characterized by global developmental delay, variable intellectual disability, impaired speech development, and behavioral abnormalities, most commonly on the autism spectrum. About half of patients develop seizures; brain imaging is typically normal. Additional features are highly variable, but may include chronic constipation, walking difficulties, and dysmorphic facial features (summary by Guo et al., 2019; pubmed:31616000). [from MIM:618906; 2020.07.24]
IDDALDS is caused by heterozygous mutation in the TANC2 gene. [from MIM:618906; 2020.07.24]
The TANC2 gene encodes a synaptic scaffolding protein that interacts with other proteins at the postsynaptic density to regulate dendritic spines and excitatory synapse formation features (summary by Guo et al., 2019; pubmed:31616000). [from MIM:618906; 2020.07.24]
Many to one: 2 human genes to 1 Drosophila gene; the second human gene is TANC1.
Moderate-scoring ortholog of human TANC2 and TANC1 (1 Drosophila to 2 human). Dmel\rols shares 38% identity and 54% similarity with the human genes.
