Whole genome sequencing of a severely affected dizygotic twin with an autism spectrum disorder and intellectual disability revealed a compound heterozygous mutation in the HTR7 gene as the only variation not detected in control databases. Each parent carries one allele of the mutation, which is not present in an unaffected stepsister. The HTR7 gene encodes the 5-HT7 serotonin receptor that is involved in brain development, synaptic transmission, and plasticity. The paternally inherited p.W60C variant is situated at an evolutionary conserved nucleotide and predicted damaging by Polyphen2. A mutation akin to the maternally inherited pV286I mutation has been reported to significantly affect the binding characteristics of the receptor. Therefore, the observed sequence alterations provide a first suggestive link between a genetic abnormality in the HTR7 gene and a neurodevelopmental disorder. © 2016 Wiley Periodicals, Inc.

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Keywords autism, dizygotic twin, HTR7, intellectual disability, serotonin receptor
Persistent URL dx.doi.org/10.1002/ajmg.b.32473, hdl.handle.net/1765/97210
Journal American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Helsmoortel, C. (Céline), Swagemakers, S.M.A, Vandeweyer, G, Stubbs, A, Palli, D, Mortier, G, … van der Spek, P.J. (2016). Whole genome sequencing of a dizygotic twin suggests a role for the serotonin receptor HTR7 in autism spectrum disorder. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 171(8), 1049–1056. doi:10.1002/ajmg.b.32473