ZDHHC15 as a candidate gene for autism spectrum disorder

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 C...

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Bibliographic Details
Published in:American journal of medical genetics. Part A 2023-04, Vol.191 (4), p.941-947
Main Authors: Casellas‐Vidal, Dolors, Mademont‐Soler, Irene, Sánchez, Joana, Plaja, Alberto, Castells, Neus, Camós, Maria, Nieto‐Moragas, Javier, Mar García, Maria, Rodriguez‐Solera, Celia, Rivera, Helena, Brunet, Joan, Álvarez, Sara, Perapoch, Josep, Queralt, Xavier, Obón, María
Format: Article
Language:English
Subjects:
Animal models
Animals
Autism
autism spectrum disorder
Autism Spectrum Disorder - genetics
Chromosome deletion
chromosome Xq13.3q21.1 deletion
Chromosomes
Cognitive ability
Exome Sequencing
Female
Genetic diversity
Haploinsufficiency
Intellectual disabilities
Karyotypes
Mental Retardation, X-Linked
Neurodevelopmental disorders
Phenotype
Phenotypes
ZDHHC15
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Summary: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.
ISSN:1552-4825
1552-4833
DOI:10.1002/ajmg.a.63099