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Exome Sequencing of a Multiplex Family with Autistic Spectrum Disorder

Friday, 3 May 2013: 09:00-13:00
Banquet Hall (Kursaal Centre)
B. Tawil1, A. H. Adi1, M. Aldosari2, M. Nester3, H. M. ALDhalaan3, E. Naim1, D. Monies1, M. Ghannam4, B. F. Meyer1 and N. Al Tassan1, (1)Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, (2)Mercy Pediatric Neurology and Psychiatry Center, Des Moines, IA, (3)Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, (4)Centre for Autism Research, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

Autistic Spectrum Disorders (ASD) represents a genetically complex developmental disorder.  Several approaches have been used to find candidate genes linked to/ or associated with ASD.  These include genome wide scans, linkage studies of multiplex families, cytogenetic studies and copy number variation [CNV].  These different approaches have yielded a number of associated and susceptible genes and high risk loci.  Single base pair substitutions in NLGN3, NLGN4 and SHANK3 genes were identified in rare cases of ASD with different degrees of severity. 


Utilize next generation sequencing (exome sequencing) in highly inbred families with three or more affected members to identify variants associated with ASD.


This is a report of one of the families from an approved collaborative research project of multiplex ASD families in Saudi Arabia. Large, highly inbred families with more than three affected members were enrolled after exclusion of the known genetic and metabolic etiologies.   Exome sequencing was performed in one affected individual, variants identified were selected based on predicted pathogenicity and screened in all family members for validation and segregation.


Whole exome sequencing identified 23 potential pathogenic novel variants in 20 genes.  These variants were screened in all family members. Only 2 changes noted in the gene HNRNPK, Exon 9 in which there was a heterozygous insertion (INS c.641[-/T] ) and another heterozygous deletion (DEL c. 519-93 [G/-]), and a missense variant T129I (c.386 C>T) in ERCC8 segregated with the disease in family members.   


The current report supports the heterogeneity of the genetic basis of ASD and the possible interaction of more than one gene on different chromosomes in the same family.

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