title: RYR2, PTDSS1 and AREG genes are implicated in a Lebanese population-based study of copy number variation in autism.
abstract: Autism Spectrum Disorders (ASDs) are a group of neurodevelopmental disorders characterized by ritualistic-repetitive behaviors and impaired verbal and non-verbal communication. Objectives were to determine the contribution of genetic variation to ASDs in the Lebanese. Affymetrix Cytogenetics Whole-Genome 2.7 M and CytoScan(™) HD Arrays were used to detect CNVs in 41 Lebanese autistic children and 35 non-autistic, developmentally delayed and intellectually disabled patients. 33 normal participants were used as controls. 16 de novo CNVs and 57 inherited CNVs, including recognized pathogenic 16p11.2 duplications and 2p16.3 deletions were identified. A duplication at 1q43 classified as likely pathogenic encompasses RYR2 as a potential ASD candidate gene. This previously identified CNV has been classified as both pathogenic, and, of uncertain significance. A duplication of unknown significance at 10q11.22, proposed as a modulator for phenotypic disease expression in Rett syndrome, was also identified. The novel potential autism susceptibility genes PTDSS1 and AREG were uncovered and warrant further genetic and functional analyses. Previously described and novel genetic targets in ASD were identified in Lebanese families with autism. These findings may lead to improved diagnosis of ASDs and informed genetic counseling, and may also lead to untapped therapeutic targets applicable to Lebanese and non-Lebanese patients.
authors.affiliation: American University of Beirut Medical Center Special Kids Clinic, Neurogenetics Program and Division of Pediatric Neurology, Departments of Pediatrics and Adolescent Medicine, Lebanon.
authors.forename: Jihane
authors.initials: J
authors.lastname: Soueid
authors.affiliation: American University of Beirut Medical Center Special Kids Clinic, Neurogenetics Program and Division of Pediatric Neurology, Departments of Pediatrics and Adolescent Medicine, Lebanon.|Department of Biological and Environmental Sciences, Faculty of Science, Beirut Arab University, Lebanon.
authors.forename: Silva
authors.initials: S
authors.lastname: Kourtian
authors.affiliation: American University of Beirut Medical Center Special Kids Clinic, Neurogenetics Program and Division of Pediatric Neurology, Departments of Pediatrics and Adolescent Medicine, Lebanon.
authors.forename: Nadine J
authors.initials: NJ
authors.lastname: Makhoul
authors.affiliation: American University of Beirut Medical Center Special Kids Clinic, Neurogenetics Program and Division of Pediatric Neurology, Departments of Pediatrics and Adolescent Medicine, Lebanon.
authors.forename: Joelle
authors.initials: J
authors.lastname: Makoukji
authors.affiliation: American University of Beirut Medical Center Special Kids Clinic, Neurogenetics Program and Division of Pediatric Neurology, Departments of Pediatrics and Adolescent Medicine, Lebanon.
authors.forename: Sariah
authors.initials: S
authors.lastname: Haddad
authors.affiliation: American University of Beirut Medical Center Special Kids Clinic, Neurogenetics Program and Division of Pediatric Neurology, Departments of Pediatrics and Adolescent Medicine, Lebanon.
authors.forename: Simona S
authors.initials: SS
authors.lastname: Ghanem
authors.affiliation: Biochemistry and Molecular Genetics, American university of Beirut, Lebanon.
authors.forename: Firas
authors.initials: F
authors.lastname: Kobeissy
authors.affiliation: American University of Beirut Medical Center Special Kids Clinic, Neurogenetics Program and Division of Pediatric Neurology, Departments of Pediatrics and Adolescent Medicine, Lebanon.|Biochemistry and Molecular Genetics, American university of Beirut, Lebanon.
authors.forename: Rose-Mary
authors.initials: RM
authors.lastname: Boustany
mesh_terms: D000293:Adolescent; D066258:Amphiregulin / Q000172:deficiency / Q000235:genetics*; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D002879:Chromosomes, Human, Pair 10; D002885:Chromosomes, Human, Pair 16; D002889:Chromosomes, Human, Pair 2; D056915:DNA Copy Number Variations; D002658:Developmental Disabilities / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D017353:Gene Deletion; D015894:Genome, Human; D006801:Humans; D007861:Lebanon; D008297:Male; D019884:Nitrogenous Group Transferases / Q000172:deficiency / Q000235:genetics*; D019837:Ryanodine Receptor Calcium Release Channel / Q000172:deficiency / Q000235:genetics*
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D019837:Ryanodine Receptor Calcium Release Channel; D019884:Nitrogenous Group Transferases; C022370:phospholipid serine base exchange enzyme