Genetics of intellectual disability in consanguineous families

Hao Hu, Kimia Kahrizi, Luciana Musante, Zohreh Fattahi, Ralf Herwig, Masoumeh Hosseini, Cornelia Oppitz, Seyedeh Sedigheh Abedini, Vanessa Suckow, Farzaneh Larti, Maryam Beheshtian, Bettina Lipkowitz, Tara Akhtarkhavari, Sepideh Mehvari, Sabine Otto, Marzieh Mohseni, Sanaz Arzhangi, Payman Jamali, Faezeh Mojahedi, Maryam TaghdiriElaheh Papari, Mohammad Javad Soltani Banavandi, Saeide Akbari, Seyed Hassan Tonekaboni, Hossein Dehghani, Mohammad Reza Ebrahimpour, Ingrid Bader, Behzad Davarnia, Monika Cohen, Hossein Khodaei, Beate Albrecht, Sarah Azimi, Birgit Zirn, Milad Bastami, Dagmar Wieczorek, Gholamreza Bahrami, Krystyna Keleman, Leila Nouri Vahid, Andreas Tzschach, Jutta Gärtner, Gabriele Gillessen-Kaesbach, Jamileh Rezazadeh Varaghchi, Bernd Timmermann, Fatemeh Pourfatemi, Aria Jankhah, Wei Chen, Pooneh Nikuei, Vera M. Kalscheuer, Morteza Oladnabi, Thomas F. Wienker, Hans Hilger Ropers*, Hossein Najmabadi

*Corresponding author for this work
56 Citations (Scopus)


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.

Original languageEnglish
JournalMolecular Psychiatry
Issue number7
Pages (from-to)1027-1039
Number of pages13
Publication statusPublished - 01.07.2019

Research Areas and Centers

  • Research Area: Medical Genetics


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