Systematic characterizing of genes of autosomal recessive intellectual disability

• Applicant: Professor Dr. André Reis, since 1/2015
• Subject Area: Human Genetics ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2012 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 215859501

Prior to this study I have clinically examined and recruited 145 families with autosomal recessive intellectual disability (ARID). Supported by the on-going DFG funding, I have sequenced the index patients of 39 families using the next generation sequencing (NGS) technology. In 6 families I identified the causative mutations in already known ARMR genes; AHI1, ALDH5A1, GPR56, GCDH, CRBN, and C12ORF65. I identified the causing mutation and I proved its pathogenicity in 4 novel ARMR genes; PGAP1, PGAP2, FAR1, and EZR. Further, I identified interesting and convincing ARMR candidate genes in 15 families; HMG20A, FRRS1L, EDC3, SPATA5, ENO2, DBF4, GBF1, CDK11A/CDK11B, KIAA0586, TGFBI1I, PPFIA1, C10ORF140, ADIPOR1, UNC5A und GALNT2, ZNF366 as well as RPS13. In addition, I initiated the Consortium of Autosomal Recessive Intellectual Disability (CARID). This is an international information exchange platform that includes almost all influential groups that work with ARMR. CARID enables the validation of the relevance of candidate genes for ARID and helps further characterizing of genes and phenotypes.In the extension period of the current DFG funding I plan to exome-wide sequence further 79 index patients. The identified candidate genes are going to be prioritized based on their expres-sion, interaction partners and based on bioinformatics analyses and on literature search. The proteins are then going to be classified in specific protein complexes, signal pathway and biosynthesis cascades. Genes in whom two or more mutations in independent families are described are going to be further examined in cellular systems. These experiments would lead to a better understanding of molecular process of cognition and would help improving the genetic diagnostics. On long term, those studies are essential for therapy.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Professor Dr. Rami Abou Jamra, until 12/2014