Details

Autor(en) / Beteiligte

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

Titel

Deep sequencing reveals 50 novel genes for recessive cognitive disorders

Ist Teil von

• Nature (London), 2011-10, Vol.478 (7367), p.57-63

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. Genes in intellectual disability Although many gene defects have been identified for X-linked early-onset cognitive impairment, or intellectual disability, much less is known about genetic determinants of its autosomal recessive forms, which are more common. In a systematic attempt to shed more light on the molecular causes of the condition, homozygosity mapping, exon enrichment and next-generation sequencing were performed in 136 consanguineous families with the condition. Fifty novel candidate genes involved in intellectual disability were identified, as well as new mutations in several genes that had previously been implicated in neurological disorders. Many of the novel candidates interact with known intellectual-disability gene products and are predicted to act in processes that are vital for normal brain development and function.