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Mol Psychiatry. 2018 Jan 4. doi: 10.1038/s41380-017-0012-2. [Epub ahead of print]

Genetics of intellectual disability in consanguineous families.

Author information

1
Max-Planck-Institute for Molecular Genetics, 14195, Berlin, Germany.
2
Guangzhou Women and Children's Medical Center, 510623, Guangzhou, China.
3
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, 19857, Iran.
4
IMP-Research Institute of Molecular Pathology, 1030, Vienna, Austria.
5
Shahrood Genetic Counseling Center, Welfare Office, Semnan, 36156, Iran.
6
Mashhad Medical Genetic Counseling Center, Mashhad, 91767, Iran.
7
Shiraz Genetic Counseling Center, Welfare Office, Shiraz, Iran.
8
Pediatric Neurology Research Center, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, 15468, Iran.
9
Kinderzentrum München, Technische Universität München, 81377, München, Germany.
10
Children's Center Munich, 81377, Munich, Germany.
11
Meybod Genetics Research Center, Welfare Organization, Yazd, 89651, Iran.
12
Institute of Human Genetics, University Hospital Essen, 45122, Essen, Germany.
13
Genetikum Counseling Center, 70173, Stuttgart, Germany.
14
Institute of Human Genetics and Anthropology, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany.
15
Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, VA, 20147, USA.
16
Institute of Clinical Genetics, Technische Universität Dresden, Dresden, Germany.
17
University Medical Center, Georg August University Göttingen, 37075, Göttingen, Germany.
18
Institute of Human Genetics, University of Lübeck, 23538, Lübeck, Germany.
19
Birjand Genetic Counseling Center, Welfare Office, Birjand, Iran.
20
Sari Genetic Counseling Center, Welfare Office, Mazandaran, Iran.
21
Shiraz Genetic Counseling Center, Shiraz, 71346, Iran.
22
Berlin Institute for Medical Systems Biology, Max Delbrueck Center for Molecular Medicine, 13125, Berlin, Germany.
23
Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
24
Max-Planck-Institute for Molecular Genetics, 14195, Berlin, Germany. ropers@molgen.mpg.de.
25
Institute of Human Genetics, University Medicine, Mainz, Germany. ropers@molgen.mpg.de.
26
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, 19857, Iran. hnajm12@yahoo.com.
27
Kariminejad - Najmabadi Pathology & Genetics Centre, Tehran, 14667-13713, Iran. hnajm12@yahoo.com.

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.

PMID:
29302074
DOI:
10.1038/s41380-017-0012-2

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