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Genetics of intellectual disability in consanguineous families

Item Type:Article
Title:Genetics of intellectual disability in consanguineous families
Creators Name:Hu, H., Kahrizi, K., Musante, L., Fattahi, Z., Herwig, R., Hosseini, M., Oppitz, C., Abedini, S.S., Suckow, V., Larti, F., Beheshtian, M., Lipkowitz, B., Akhtarkhavari, T., Mehvari, S., Otto, S., Mohseni, M., Arzhangi, S., Jamali, P., Mojahedi, F., Taghdiri, M., Papari, E., Soltani Banavandi, M.J., Akbari, S., Tonekaboni, S.H., Dehghani, H., Ebrahimpour, M.R., Bader, I., Davarnia, B., Cohen, M., Khodaei, H., Albrecht, B., Azimi, S., Zirn, B., Bastami, M., Wieczorek, D., Bahrami, G., Keleman, K., Vahid, L.N., Tzschach, A., Gärtner, J., Gillessen-Kaesbach, G., Varaghchi, J.R., Timmermann, B., Pourfatemi, F., Jankhah, A., Chen, W., Nikuei, P., Kalscheuer, V.M., Oladnabi, M., Wienker, T.F., Ropers, H.H. and Najmabadi, H.
Abstract:Autosomal recessive (AR) gene defects are the leading genetic cause of intellectual disability (ID) in countries with frequent parental consanguinity, which account for about 1/7th of the world population. Yet, compared to autosomal dominant de novo mutations, which are the predominant cause of ID in Western countries, the identification of AR-ID genes has lagged behind. Here, we report on whole exome and whole genome sequencing in 404 consanguineous predominantly Iranian families with two or more affected offspring. In 219 of these, we found likely causative variants, involving 77 known and 77 novel AR-ID (candidate) genes, 21 X-linked genes, as well as 9 genes previously implicated in diseases other than ID. This study, the largest of its kind published to date, illustrates that high-throughput DNA sequencing in consanguineous families is a superior strategy for elucidating the thousands of hitherto unknown gene defects underlying AR-ID, and it sheds light on their prevalence.
Keywords:Consanguinity, Exome, Family, High-Throughput Nucleotide Sequencing, Homozygote, Intellectual Disability, Iran, Mutation, Pedigree, Protein Interaction Maps, Recessive Genes, Whole Exome Sequencing, Whole Genome Sequencing
Source:Molecular Psychiatry
Publisher:Nature Publishing Group
Page Range:1027-1039
Date:July 2019
Official Publication:https://doi.org/10.1038/s41380-017-0012-2
PubMed:View item in PubMed

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