title: Homozygosity mapping in 64 Syrian consanguineous families with non-specific intellectual disability reveals 11 novel loci and high heterogeneity.
abstract: Non-specific intellectual disability of autosomal recessive inheritance (NS-ARID) represents an important fraction of severe cognitive dysfunction disorders. To date, only 10 genes have been identified, and further 24 linked-ARID loci have been reported, as well as others with suggestive linkage. To discover novel genes causing NS-ARID, we undertook genome-wide homozygosity mapping in 64 consanguineous multiplex families of Syrian descent. A total of 11 families revealed unique, significantly linked loci at 4q26-4q28 (MRT17), 6q12-q15 (MRT18), 18p11 (MRT19), 16p12-q12 (MRT20), 11p15 (MRT21), 11p13-q14 (MRT23), 6p12 (MRT24), 12q13-q15 (MRT25), 14q11-q12 (MRT26), 15q23-q26 (MRT27), and 6q26-q27 (MRT28), respectively. Loci ranged between 1.2 and 45.6 Mb in length. One family showed linkage to chromosome 8q24.3, and we identified a mutation in TRAPPC9. Our study further highlights the extreme heterogeneity of NS-ARID, and suggests that no major disease gene is to be expected, at least in this study group. Systematic analysis of large numbers of affected families, as presented here, will help discovering the genetic causes of ID.
authors.affiliation: Institute of Human Genetics, University of Erlangen-Nuremberg, Schwabachanlage 10, Erlangen, Germany. rami.aboujamra@uk-erlangen.de
authors.forename: R
authors.initials: R
authors.lastname: Abou Jamra
authors.forename: Sigrun
authors.initials: S
authors.lastname: Wohlfart
authors.forename: Markus
authors.initials: M
authors.lastname: Zweier
authors.forename: Steffen
authors.initials: S
authors.lastname: Uebe
authors.forename: Lutz
authors.initials: L
authors.lastname: Priebe
authors.forename: Arif
authors.initials: A
authors.lastname: Ekici
authors.forename: Susanne
authors.initials: S
authors.lastname: Giesebrecht
authors.forename: Ahmad
authors.initials: A
authors.lastname: Abboud
authors.forename: Mohammed Ayman
authors.initials: MA
authors.lastname: Al Khateeb
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Fakher
authors.forename: Saber
authors.initials: S
authors.lastname: Hamdan
authors.forename: Amina
authors.initials: A
authors.lastname: Ismael
authors.forename: Safia
authors.initials: S
authors.lastname: Muhammad
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
authors.forename: André
authors.initials: A
authors.lastname: Reis
mesh_terms: D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D003241:Consanguinity; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D056426:Genetic Loci; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009154:Mutation; D010375:Pedigree; D013593:Syria; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; C503887:TRAPPC9 protein, human