Deep sequencing reveals 50 novel genes for recessive cognitive disorders

Nature. 2011 Sep 21;478(7367):57-63. doi: 10.1038/nature10423.

Hossein Najmabadi ¹, Hao Hu, Masoud Garshasbi, Tomasz Zemojtel, Seyedeh Sedigheh Abedini, Wei Chen, Masoumeh Hosseini, Farkhondeh Behjati, Stefan Haas, Payman Jamali, Agnes Zecha, Marzieh Mohseni, Lucia Püttmann, Leyla Nouri Vahid, Corinna Jensen, Lia Abbasi Moheb, Melanie Bienek, Farzaneh Larti, Ines Mueller, Robert Weissmann, Hossein Darvish, Klaus Wrogemann, Valeh Hadavi, Bettina Lipkowitz, Sahar Esmaeeli-Nieh, Dagmar Wieczorek, Roxana Kariminejad, Saghar Ghasemi Firouzabadi, Monika Cohen, Zohreh Fattahi, Imma Rost, Faezeh Mojahedi, Christoph Hertzberg, Atefeh Dehghan, Anna Rajab, Mohammad Javad Soltani Banavandi, Julia Hoffer, Masoumeh Falah, Luciana Musante, Vera Kalscheuer, Reinhard Ullmann, Andreas Walter Kuss, Andreas Tzschach, Kimia Kahrizi, H Hilger Ropers

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Affiliation

1 Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, 19857 Tehran, Iran.

PMID: 21937992 DOI: 10.1038/nature10423

Abstract

Common diseases are often complex because they are genetically heterogeneous, with many different genetic defects giving rise to clinically indistinguishable phenotypes. This has been amply documented for early-onset cognitive impairment, or intellectual disability, one of the most complex disorders known and a very important health care problem worldwide. More than 90 different gene defects have been identified for X-chromosome-linked intellectual disability alone, but research into the more frequent autosomal forms of intellectual disability is still in its infancy. To expedite the molecular elucidation of autosomal-recessive intellectual disability, we have now performed homozygosity mapping, exon enrichment and next-generation Sequencing in 136 consanguineous families with autosomal-recessive intellectual disability from Iran and elsewhere. This study, the largest published so far, has revealed additional mutations in 23 genes previously implicated in intellectual disability or related neurological disorders, as well as single, probably disease-causing variants in 50 novel candidate genes. Proteins encoded by several of these genes interact directly with products of known intellectual disability genes, and many are involved in fundamental cellular processes such as transcription and translation, cell-cycle control, energy metabolism and fatty-acid synthesis, which seem to be pivotal for normal brain development and function.

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