Variability in autism spectrum phenotypes linked to heterozygous missense familial ANK2 mutation

Abstract

Autism Spectrum Disorder (ASD) is to date considered a disorder with a complex aetiology that recognizes both genetic and environmental risk factors. The role of the genetic contribution is progressively and significantly increasing, and lately thousands of genes have been linked to ASD. In this clinical report we describe a child with ASD carrying a heterozygous novel missense variant p.Arg987Trp in the ANK2 gene in heterozygous state, predicted pathogenic, and inherited from her father. The ANK2 gene has been associated with ASD but to date just few reports described the related phenotypes thus we aim at expanding behaviours endophenotypes of familial ANK2-related condition. Our patient was diagnosed with high-functioning ASD while her father showed subthreshold autistic traits such as relational difficulties and peculiar interests. We present this familial case to study genotype-phenotype correlation and highlight the huge variability of Autism spectrum phenotypes of the ANK2-related conditions. Nevertheless, future studies that can explore more of the link between the genetics of autism and associated clinical expressivity would be interesting.