title: Deep sequencing reveals 50 novel genes for recessive cognitive disorders.
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.
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, 19857 Tehran, Iran.
authors.forename: Hossein
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authors.lastname: Najmabadi
authors.forename: Hao
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authors.lastname: Hu
authors.forename: Masoud
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authors.lastname: Garshasbi
authors.forename: Tomasz
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authors.forename: Seyedeh Sedigheh
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authors.lastname: Abedini
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authors.lastname: Chen
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authors.forename: Lia Abbasi
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authors.lastname: Moheb
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authors.forename: Farzaneh
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authors.lastname: Larti
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authors.lastname: Mueller
authors.forename: Robert
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authors.lastname: Weissmann
authors.forename: Hossein
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authors.lastname: Darvish
authors.forename: Klaus
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authors.lastname: Wrogemann
authors.forename: Valeh
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authors.forename: Bettina
authors.initials: B
authors.lastname: Lipkowitz
authors.forename: Sahar
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authors.lastname: Esmaeeli-Nieh
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wieczorek
authors.forename: Roxana
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authors.lastname: Kariminejad
authors.forename: Saghar Ghasemi
authors.initials: SG
authors.lastname: Firouzabadi
authors.forename: Monika
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authors.lastname: Cohen
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Fattahi
authors.forename: Imma
authors.initials: I
authors.lastname: Rost
authors.forename: Faezeh
authors.initials: F
authors.lastname: Mojahedi
authors.forename: Christoph
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authors.lastname: Hertzberg
authors.forename: Atefeh
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authors.lastname: Dehghan
authors.forename: Anna
authors.initials: A
authors.lastname: Rajab
authors.forename: Mohammad Javad Soltani
authors.initials: MJ
authors.lastname: Banavandi
authors.forename: Julia
authors.initials: J
authors.lastname: Hoffer
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Falah
authors.forename: Luciana
authors.initials: L
authors.lastname: Musante
authors.forename: Vera
authors.initials: V
authors.lastname: Kalscheuer
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ullmann
authors.forename: Andreas Walter
authors.initials: AW
authors.lastname: Kuss
authors.forename: Andreas
authors.initials: A
authors.lastname: Tzschach
authors.forename: Kimia
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authors.lastname: Kahrizi
authors.forename: H Hilger
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authors.lastname: Ropers
mesh_terms: D001921:Brain / Q000378:metabolism / Q000502:physiology; D002453:Cell Cycle; D003072:Cognition Disorders / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D053263:Gene Regulatory Networks; D020043:Genes, Essential / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D053858:Metabolic Networks and Pathways; D009154:Mutation / Q000235:genetics; D009928:Organ Specificity; D013569:Synapses / Q000378:metabolism