Effect of inbreeding on intellectual disability revisited by trio sequencing
| Autor: | Payman Jamali, Zhila Ghaderi, Hans-Hilger Ropers, Haleh Habibi, Fatemeh Pourfatemi, Farahnaz Sabbagh Kermani, Zohreh Mehrjoo, Kimia Kahrizi, Farnaz Sadeghinia, Hao Hu, Vera M. Kalscheuer, Bettina Lipkowitz, Reza Najafipour, Sanaz Arzhangi, Maryam Rahimi, Pooneh Nikuei, Atefeh Khoshaeen, Marzieh Mohseni, Masoumeh Hosseini, Hossein Najmabadi, Vanessa Suckow, Milad Falahat Chian, Faezeh Mojahedi, Sepideh Mehvari, Zohreh Fattahi, Maryam Beheshtian, Roshanak Jazayeri, Mohammad-Reza Khodaie-Ardakani, S. Hassan Tonekaboni, Tara Akhtarkhavari, Thomas F. Wienker |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Genes Recessive Iran 030105 genetics & heredity Biology Carrier testing Consanguinity Middle East 03 medical and health sciences Intellectual Disability Exome Sequencing Intellectual disability Genetics medicine Humans Exome Family Inbreeding Genetics (clinical) De novo mutations Exome sequencing High rate Homozygote Disease gene identification medicine.disease Pedigree 030104 developmental biology Parental consanguinity Mutation Female |
| Zdroj: | Clinical Genetics: an international journal of genetics in medicine |
| ISSN: | 1399-0004 0009-9163 |
| DOI: | 10.1111/cge.13463 |
| Popis: | In outbred Western populations, most individuals with intellectual disability (ID) are sporadic cases, dominant de novo mutations (DNM) are frequent, and autosomal recessive ID (ARID) is very rare. Due to the high rate of parental consanguinity which raises the risk for ARID and other recessive disorders, the prevalence of ID is significantly higher in Near- and Middle-East countries. Indeed, homozygosity mapping and sequencing in consanguineous families have already identified a plethora of ARID genes, but due to the design of these studies, DNMs could not be systematically assessed, and the proportion of cases that are potentially preventable by avoiding consanguineous marriages or through carrier testing is hitherto unknown. This prompted us to perform whole exome sequencing in 100 sporadic ID patients from Iran and their healthy consanguineous parents. In 61 patients, we identified apparently causative changes in known ID genes. Of these, 44 were homozygous recessive and 17 dominant de novo mutations. Assuming that the DNM rate is stable, these results suggest that parental consanguinity raises the ID risk about 3.6-fold, and about 4.1-4.25-fold for children of first-cousin unions. These results do not rhyme with recent opinions that consanguinity-related health risks are generally small and have been 'overstated' in the past. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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