• Billuart-type X-linked syndromic intellectual developmental disorder

This report describe 'intellectual developmental disorder, X-linked, syndromic, Billuart type', a form of syndromic intellectual disability; the disease exhibits X-linked recessive inheritance. The human gene implicated in this disease is OPHN1, a Rho-GTPase-activating protein that plays a number of roles in synaptic function. There is a single orthologous gene in Drosophila, Graf, for which multiple genetic reagents have been generated, including an amorphic allele, UAS constructs, RNAi-targeting constructs, and alleles caused by insertional mutagenesis. Dmel\Graf is orthologous to 3 other genes in human, ARHGAP26, ARHGAP42, ARHGAP10.

A UAS construct of the human Hsap\OPHN1 gene has been introduced into flies. Partial heterologous rescue (functional complementation) has been demonstrated for the defects in development the mushroom body observed for Dmel\Graf loss-of-function mutations.

Animals hemizygous for Dmel\Graf exhibit impairment in long-term olfactory memory; short-term memory and intermediate-term memory appear to form normally. Loss of Graf impacts development of the mushroom body, a key brain structure for learning and memory, causing abnormal crossing and apparent fusion of the mushroom body β lobe over the brain midline. Physical and genetic interactions have been report for Dmel\Graf; see below and in the Graf gene report.

[updated April 2025 by FlyBase; FBrf0222196]