This report describes intellectual disability, X-linked syndromic 34, an X-linked recessive neurodevelopmental disorder. The human gene implicated in this disease is NONO, a nuclear protein involved in various aspects of RNA metabolism. There are two high-scoring Drosophila orthologs, Dmel\nonA and Dmel\nonA-l. Multiple genetic reagents, including amorphic and loss-of-function alleles, alleles caused by insertional mutagenesis, and RNAi-targeting constructs have been generated for Dmel\nonA.
UAS constructs of Hsap\NONO have been introduced into flies, including wild-type and a variant associated with disease. See the 'Disease-Implicated Variants' table below.
Targeted overexpression of both wild-type Dmel\nonA and Hsap\NONO in the developing eye result in a rough eye phenotype. This phenotype is less pronounced for Hsap\NONO bearing the disease-implicated variant Pro459Ala.
[updated Feb. 2023 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 34; MRXS34](https://omim.org/entry/300967)
[NON-POU DOMAIN-CONTAINING OCTAMER-BINDING PROTEIN; NONO](https://omim.org/entry/300084)
Intellectual disability, X-linked syndromic 34 (MRXS34) is an X-linked recessive neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability with poor speech, dysmorphic facial features, and mild structural brain abnormalities, including thickening of the corpus callosum (summary by Mircsof et al., 2015, pubmed:26571461). Several variants in the causative gene are additionally associated with cardiac phenotypes (Reinstein et al., 2016, pubmed:27329731,; Scott et al., 2017, pubmed:27550220; Carlston et al., 2019, pubmed:30773818) [from MIM:300967; 2023.02.08]
Intellectual disability, X-linked syndromic 34 is caused by mutation in the NONO gene on chromosome Xq16. [from MIM:300967; 2023.02.08]
Hemizgous loss-of-function variants in NONO cause X-linked syndromic intellectual developmental disorder-34 (Itai, et al., 2023 pubmed:36653413, FBrf0255543).
The NONO gene encodes a protein that belongs to the highly conserved Drosophila behavior/human splicing (DBHS) protein family. This family includes 3 members in mammals: NONO, PSPC1, and SFPQ. DBHS proteins are nuclear proteins involved in various aspects of RNA metabolism (summary by Mircsof et al., 2015, pubmed:26571461). [from MIM:300084; 2023.02.08]
High-scoring ortholog of human TSFPQ, NONO, PSPSC1 (2 Drosophila to many human).
High-scoring ortholog of human SFPQ, NONO, PSPSC1 (2 Drosophila to many human).
