title: Whole genome sequencing of a dizygotic twin suggests a role for the serotonin receptor HTR7 in autism spectrum disorder.
abstract: 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-HT7serotonin 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.
authors.affiliation: Department of Medical Genetics, University and University Hospital of Antwerp, Edegem, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Helsmoortel
authors.affiliation: Department of Bioinformatics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Sigrid M A
authors.initials: SM
authors.lastname: Swagemakers
authors.affiliation: Department of Medical Genetics, University and University Hospital of Antwerp, Edegem, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Vandeweyer
authors.affiliation: Department of Bioinformatics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Stubbs
authors.affiliation: Department of Bioinformatics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Ivo
authors.initials: I
authors.lastname: Palli
authors.affiliation: Department of Medical Genetics, University and University Hospital of Antwerp, Edegem, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Mortier
authors.affiliation: Department of Medical Genetics, University and University Hospital of Antwerp, Edegem, Belgium.
authors.forename: R Frank
authors.initials: RF
authors.lastname: Kooy
authors.affiliation: Department of Bioinformatics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van der Spek
mesh_terms: D000483:Alleles; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000378:metabolism; D001321:Autistic Disorder / Q000235:genetics; D002648:Child; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D011985:Receptors, Serotonin / Q000235:genetics* / Q000502:physiology; D017422:Sequence Analysis, DNA; D012701:Serotonin / Q000235:genetics / Q000378:metabolism; D014429:Twins, Dizygotic / Q000235:genetics / Q000523:psychology
chemical_list: D011985:Receptors, Serotonin; C104425:serotonin 7 receptor; D012701:Serotonin
keywords: HTR7; autism; dizygotic twin; intellectual disability; serotonin receptor