title: A complex Xp11.22 deletion in a patient with syndromic autism: exploration of FAM120C as a positional candidate gene for autism.
abstract: We present a male patient with sporadic Aarskog syndrome, cleft palate, mild intellectual disability, and autism spectrum disorder (ASD). A submicroscopic discontiguous deletion was detected on chromosome Xp11.2 encompassing FGD1, FAM120C, and PHF8. That the deletion encompassed FGD1 (exons 2-8) explains the Aarskog features while the deletion of PHF8 most likely explains the cleft palate and mild intellectual disability. We identify FAM120C as a novel X-linked candidate gene for autism for two reasons: first, a larger deletion encompassing FAM120C segregates with autism in a previously reported family and second, there is recent evidence that FAM120C interacts with CYFIP1, part of the FMRP (Fragile X Mental Retardation Protein) network. In the current study, resequencing of FAM120C in 87 Belgian male patients with autism spectrum disorder identified no novel mutations. Expression of Fam120c in mouse tissues showed enriched expression in pituitary, cerebellum, cortex, and pancreatic islets of Langerhans. Additionally, we found a cortical expression pattern of Fam120c similar to that of Fmr1. In conclusion, FAM120C is a novel candidate gene for autism spectrum disorder based on genetic evidence and the brain expression pattern. Thereby we highlight a role for FMRP network genes in ASD.
authors.affiliation: Center for Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium; Leuven Autism Research (LAuRes), KU Leuven, Leuven, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: De Wolf
authors.forename: An
authors.initials: A
authors.lastname: Crepel
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
authors.forename: Leentje
authors.initials: L
authors.lastname: van Lommel
authors.forename: Berten
authors.initials: B
authors.lastname: Ceulemans
authors.forename: Jean
authors.initials: J
authors.lastname: Steyaert
authors.forename: Eve
authors.initials: E
authors.lastname: Seuntjens
authors.forename: Hilde
authors.initials: H
authors.lastname: Peeters
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004392:Dwarfism / Q000235:genetics*; D005145:Face / Q000002:abnormalities*; D020869:Gene Expression Profiling; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D005837:Genitalia, Male / Q000002:abnormalities*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006228:Hand Deformities, Congenital / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000235:genetics*; D056466:Histone Demethylases / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D007621:Karyotyping; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics
chemical_list: D017931:DNA Primers; C480630:FAM120C protein, human; C490796:FGD1 protein, human; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D014157:Transcription Factors; D056466:Histone Demethylases; C511934:PHF8 protein, human
keywords: FAM120C; X-linked; autism spectrum disorder; candidate gene; deletion