Homozygosity mapping in 64 Syrian consanguineous families with non-specific intellectual disability reveals 11 novel loci and high heterogeneity

作者：Abou Jamra Rami^*; Wohlfart Sigrun; Zweier Markus; Uebe Steffen; Priebe Lutz; Ekici Arif; Giesebrecht Susanne; Abboud Ahmad; Al Khateeb Mohammed Ayman; Fakher Mahmoud; Hamdan Saber; Ismael Amina; Muhammad Safia; Noethen Markus M; Schumacher Johannes; Reis Andre

来源：European Journal of Human Genetics, 2011, 19(11): 1161-1166.

DOI：10.1038/ejhg.2011.98

• non-specific
• mental retardation
• microcephaly
• epilepsy
• MRT

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 45.6Mb 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. European Journal of Human Genetics (2011) 19, 1161-1166; doi:10.1038/ejhg.2011.98; published online 1 June 2011

• 出版日期2011-11