title: Candidate Genes for Inherited Autism Susceptibility in the Lebanese Population.
abstract: Autism spectrum disorder (ASD) is characterized by ritualistic-repetitive behaviors and impaired verbal/non-verbal communication. Many ASD susceptibility genes implicated in neuronal pathways/brain development have been identified. The Lebanese population is ideal for uncovering recessive genes because of shared ancestry and a high rate of consanguineous marriages. Aims here are to analyze for published ASD genes and uncover novel inherited ASD susceptibility genes specific to the Lebanese. We recruited 36 ASD families (ASD: 37, unaffected parents: 36, unaffected siblings: 33) and 100 unaffected Lebanese controls. Cytogenetics 2.7 M Microarrays/CytoScan™ HD arrays allowed mapping of homozygous regions of the genome. The CNTNAP2 gene was screened by Sanger sequencing. Homozygosity mapping uncovered DPP4, TRHR, and MLF1 as novel candidate susceptibility genes for ASD in the Lebanese. Sequencing of hot spot exons in CNTNAP2 led to discovery of a 5 bp insertion in 23/37 ASD patients. This mutation was present in unaffected family members and unaffected Lebanese controls. Although a slight increase in number was observed in ASD patients and family members compared to controls, there were no significant differences in allele frequencies between affecteds and controls (C/TTCTG: γ2value = 0.014; p = 0.904). The CNTNAP2 polymorphism identified in this population, hence, is not linked to the ASD phenotype.
authors.affiliation: American University of Beirut Medical Center Special Kids Clinic, Neurogenetics Program and Division of Pediatric Neurology, 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, 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, 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, Lebanon.
authors.forename: Dikran Richard
authors.initials: DR
authors.lastname: Guisso
authors.affiliation: Eugene McDermott Center for Human Growth and Development, Departments of Neuroscience and Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Chahrour
authors.affiliation: American University of Beirut Medical Center Special Kids Clinic, Neurogenetics Program and Division of Pediatric Neurology, Lebanon.|Biochemistry and Molecular Genetics, American university of Beirut, Lebanon.
authors.forename: Rose-Mary N
authors.initials: RN
authors.lastname: Boustany
mesh_terms: D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000235:genetics*; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004268:DNA-Binding Proteins; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006720:Homozygote; D006801:Humans; D007861:Lebanon; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D016254:Mutagenesis, Insertional; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: C403049:CNTNAP2 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C100852:MLF1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D018025:Receptors, Thyrotropin-Releasing Hormone; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4