ZDHHC15 as a candidate gene for autism spectrum disorder

Abstract

The phenotypic repercussion of ZDHHC15 haploinsufficiency is not well-known. This gene was initially suggested as a candidate for X-linked mental retardation, but such an association was later questioned. We studied a multiplex family with three members with autism spectrum disorder (ASD) by array CGH, karyotype, exome sequencing and X-chromosome inactivation patterns. Medical history interviews, cognitive and physical examinations, and sensory profiling were also assessed. The three family members with ASD (with normal cognitive abilities and an abnormal sensory profile) were the only carriers of a 1.7 Mb deletion in the long arm of chromosome X, involving: ZDHHC15, MAGEE2, PBDC1, MAGEE1, MIR384 and MIR325. The normal chromosome X was preferentially inactivated in female carriers, and the whole exome sequencing of an affected family member did not reveal any additional genetic variant that could explain the phenotype. Thus, in the present family, ASD segregates with a deletion on chromosome X that includes ZDHHC15. Considering our results together with gene data (regarding function, expression, conservation and animal/ cellular models), ZDHHC15 is a candidate gene for ASD. Emerging evidence also suggests that this gene could be associated with other neurodevelopmental disorders, with incomplete penetrance and variable expressivity.

Neuroplasticity of children in autism spectrum disorder

“…Most ASD-related genes determine the function of the nervous system and affect certain protein activities and cellular functions in genetic information propagation, such as disruption of protein localization on the mitotic spindle, cell cycle arrest, DNA damage and cell death ( 19 ). In terms of single genes, haploinsufficiency in KMT2E ( 20 ), Taok1 ( 21 ), PLPPR4 ( 22 ), ZDHHC15 ( 23 ), ASH1L ( 24 ), and Kdm6b ( 25 )affects neurological development and produces ASD symptoms. The CAPRIN1 gene is critical for synaptic plasticity, encoding a ubiquitous protein regulating mRNA transport and translation.…”

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

“…Recently, zDHHC15 has been recognized as a candidate gene for autism spectrum disorder (ASD). New evidence also suggests that this gene may be associated with other neurodevelopmental disorders ( Casellas-Vidal et al, 2023 ). zDHHC8 may be associated with epileptic seizures in humans, and knockdown of zDHHC8 may have anti-epileptogenic effects on drug-resistant epilepsy.…”

“…Frontiers in Pharmacology frontiersin.org disorders (Casellas-Vidal et al, 2023). zDHHC8 may be associated with epileptic seizures in humans, and knockdown of zDHHC8 may have anti-epileptogenic effects on drug-resistant epilepsy.…”