Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jul;24(7):1027-1039.
doi: 10.1038/s41380-017-0012-2. Epub 2018 Jan 4.

Genetics of intellectual disability in consanguineous families

Hao Hu #  1   2 , Kimia Kahrizi #  3 , Luciana Musante  1 , Zohreh Fattahi  3 , Ralf Herwig  1 , Masoumeh Hosseini  3 , Cornelia Oppitz  4 , Seyedeh Sedigheh Abedini  3 , Vanessa Suckow  1 , Farzaneh Larti  3 , Maryam Beheshtian  3 , Bettina Lipkowitz  1 , Tara Akhtarkhavari  3 , Sepideh Mehvari  3 , Sabine Otto  1 , Marzieh Mohseni  3 , Sanaz Arzhangi  3 , Payman Jamali  5 , Faezeh Mojahedi  6 , Maryam Taghdiri  7 , Elaheh Papari  3 , Mohammad Javad Soltani Banavandi  3 , Saeide Akbari  3 , Seyed Hassan Tonekaboni  8 , Hossein Dehghani  3 , Mohammad Reza Ebrahimpour  3 , Ingrid Bader  9 , Behzad Davarnia  3 , Monika Cohen  10 , Hossein Khodaei  11 , Beate Albrecht  12 , Sarah Azimi  3 , Birgit Zirn  13 , Milad Bastami  3 , Dagmar Wieczorek  14 , Gholamreza Bahrami  3 , Krystyna Keleman  4   15 , Leila Nouri Vahid  3 , Andreas Tzschach  1   16 , Jutta Gärtner  17 , Gabriele Gillessen-Kaesbach  18 , Jamileh Rezazadeh Varaghchi  19 , Bernd Timmermann  1 , Fatemeh Pourfatemi  20 , Aria Jankhah  21 , Wei Chen  22 , Pooneh Nikuei  23 , Vera M Kalscheuer  1 , Morteza Oladnabi  3 , Thomas F Wienker  1 , Hans-Hilger Ropers #  24   25 , Hossein Najmabadi #  26   27
Affiliations

Genetics of intellectual disability in consanguineous families

Hao Hu et al. Mol Psychiatry. 2019 Jul.

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.

PubMed Disclaimer

References

    1. Shaw-Smith C, Redon R, Rickman L, Rio M, Willatt L, Fiegler H, et al. Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features. J Med Genet. 2004;41:241–8. - PubMed - PMC
    1. Gilissen C, Hehir-Kwa JY, Thung DT, van de Vorst M, van Bon BW, Willemsen MH, et al. Genome sequencing identifies major causes of severe intellectual disability. Nature. 2014;511:344–7.
    1. Vissers LE, de Ligt J, Gilissen C, Janssen I, Steehouwer M, de Vries P, et al. A de novo paradigm for mental retardation. Nat Genet. 2010;42:1109–12.
    1. Ropers HH. Genetics of early onset cognitive impairment. Annu Rev Genom Hum Genet. 2010;11:161–87.
    1. Musante L, Ropers HH. Genetics of recessive cognitive disorders. Trends Genet. 2014;30:32–39. - PubMed

Publication types