This report describes intellectual disability, X-linked syndromic, Claes-Jensen type; an alternative designation of this disease is 'mental retardation, X-linked syndromic, Claes-Jensen type' (MRXSCJ). MRXSCJ exhibits X-linked recessive inheritance. The human gene implicated in this disease is KDM5C, which encodes a histone demethylase thought to be involved in the regulation of transcription and chromatin remodeling; it is one of 4 closely related genes in human. The human KDM5B gene is implicated in a subtype of intellectual disability (MIM:618109). There is a single orthologous gene in Drosophila, Kdm5, for which an amorphic mutation, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
The human KDM5C gene has not been introduced into flies.
This disease has been modeled in flies by introducing into Dmel\Kdm5 transgenes mutational changes analogous to those implicated in MRXSCJ. See the 'Disease-Implicated Variants' table below. In a background genotype that is amorphic for Kdm5, animals carrying the A512P missense mutation (analogous to KDM5C:p.Ala388Pro ) are viable and fertile but exhibit short-term and long-term memory deficits. Other variants implicated in MRXSCJ have been assessed for impact on development of the larval neuromuscular junction. In general, the disease-associated mutations disrupt neuroanatomical development, cognition and other behaviors, and display a transcriptional signature characterized by the downregulation of many ribosomal protein genes.
[updated Nov. 2024 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, CLAES-JENSEN TYPE; MRXSCJ](https://omim.org/entry/300534)
[LYSINE DEMETHYLASE 5C; KDM5C](https://omim.org/entry/314690)
MRXSCJ is characterized by severe intellectual deficit associated with variable clinical manifestations including spasticity, cryptorchidism, maxillary hypoplasia, alopecia areata, epilepsy, short stature, impaired speech and behavioral problems (DOID:0060809).
MRXSCJ exhibits X-linked recessive inheritance; caused by mutation in the KDM5C gene. [from MIM:300534; 2018.07.19]
KDM5C, also known as JARID1C, encodes a histone demethylase that specifically demethylates Lys-4 of histone H3; its DNA-binding motifs suggest this protein is involved in the regulation of transcription and chromatin remodeling. [Gene Cards, KDM5C; 2018.07.20]
Many to one: 4 human to 1 fly.
Moderate- to high-scoring ortholog of human KDM5A, KDM5B, KDM5C, and KDM5D (1 Drosophila to 4 human). Dmel\Kdm5 shares 39-42% identity and 53-57% similarity with the human genes.
