Impaired Face Recognition in Parents and Siblings of Children with ASD: a Differential Sex Effect

David H. Skuse, MD, Gemma Salter, and Anna Seigal. Behavioural and Brain Sciences, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, United Kingdom

Background:  The heterogeneity of the phenotype suggests that autism has a multigenic aetiology. Our understanding of the complex multigenic aetiology of autistic spectrum disorders (ASD) may be increased by family studies of the broader autism phenotype, measured at the level of heritable endophenotypic variation in specific cognitive skills.

Objectives: Our objective was to identify heritable markers of genetic susceptibility among families containing a single child with an ASD. We aimed to use standardized measures of cognitive function in the social domain, which had been developed from studies of the general population and which would be applicable to both children and adults. Our focus was on potential X-linked genes that confer vulnerability to males.

Methods: All participants were tested on a standardized task of face recognition memory.  Case families (82 autistic probands, 179 parents, and 67 siblings) were closely matched to population controls, and to a second comparison group of women with X-monosomy (Turner syndrome) which is associated with autistic behaviours. Families with an autistic child and X-monosomic females were assessed for autistic traits by self-report. The second comparison group comprised 151 adult females with X-monosomy, of similar verbal IQ to control females. Results: Autistic probands, their mothers and brothers showed a significant deficit in face recognition memory, compared to controls. In X-monosomic females face recognition memory was much poorer than in population control females. 

Conclusions:This is the first study to find evidence for an autism-related endophenotype that is present in mothers, their male autistic offspring and brothers of those offspring, but which is less evident in fathers and absent in female siblings. We present preliminary evidence pointing to inheritance of a genetic risk for face-recognition memory that is X-linked.



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