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 Taghdiri; Elaheh 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

doi:10.1038/s41380-017-0012-2

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

^*Korrespondierende/r Autor/-in für diese Arbeit

Institut für Humangenetik

167 Zitate (Scopus)

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.

Originalsprache	Englisch
Zeitschrift	Molecular Psychiatry
Jahrgang	24
Ausgabenummer	7
Seiten (von - bis)	1027-1039
Seitenumfang	13
ISSN	1359-4184
DOIs	https://doi.org/10.1038/s41380-017-0012-2
Publikationsstatus	Veröffentlicht - 01.07.2019

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Acknowledgements We are grateful to all patients and families for their participation in this study, S. Banihashemi and Kh. Jalalvand for technical support and Gabriele Eder for assisting us with the preparation of the manuscript. We would also like to thank the NHLBI GO Exome Sequencing Project and its ongoing studies, as well as the Exome Aggregation Consortium and the groups that provided exome variant data for comparison. A full list of contributing groups can be found at http://exac.broadinstitute.org/about. This research was supported by the European Union through FP7 project GENCODYS, grant no 241995 (organizer: Hans van Bokhoven), the Max Planck Innovation Funds and the Ministry of Health and Medical Education, Islamic Republic Iran. Additional support was received from the Iranian National Science Foundation (grant no.s 92038458 and 92035782), the Iranian National Elite Foundation and the Iranian Science Elite Federation.

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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., ... Najmabadi, H. (2019). Genetics of intellectual disability in consanguineous families. Molecular Psychiatry, 24(7), 1027-1039. https://doi.org/10.1038/s41380-017-0012-2

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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.",

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

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Hu, H, Kahrizi, K, Musante, L, Fattahi, Z, Herwig, R, Hosseini, M, Oppitz, C, Abedini, SS, 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, MJ, Akbari, S, Tonekaboni, SH, Dehghani, H, Ebrahimpour, MR, Bader, I, Davarnia, B, Cohen, M, Khodaei, H, Albrecht, B, Azimi, S, Zirn, B, Bastami, M, Wieczorek, D, Bahrami, G, Keleman, K, Vahid, LN, Tzschach, A, Gärtner, J, Gillessen-Kaesbach, G, Varaghchi, JR, Timmermann, B, Pourfatemi, F, Jankhah, A, Chen, W, Nikuei, P, Kalscheuer, VM, Oladnabi, M, Wienker, TF, Ropers, HH & Najmabadi, H 2019, 'Genetics of intellectual disability in consanguineous families', Molecular Psychiatry, Jg. 24, Nr. 7, S. 1027-1039. https://doi.org/10.1038/s41380-017-0012-2

TY - JOUR

T1 - Genetics of intellectual disability in consanguineous families

AU - Hu, Hao

AU - Kahrizi, Kimia

AU - Musante, Luciana

AU - Fattahi, Zohreh

AU - Herwig, Ralf

AU - Hosseini, Masoumeh

AU - Oppitz, Cornelia

AU - Abedini, Seyedeh Sedigheh

AU - Suckow, Vanessa

AU - Larti, Farzaneh

AU - Beheshtian, Maryam

AU - Lipkowitz, Bettina

AU - Akhtarkhavari, Tara

AU - Mehvari, Sepideh

AU - Otto, Sabine

AU - Mohseni, Marzieh

AU - Arzhangi, Sanaz

AU - Jamali, Payman

AU - Mojahedi, Faezeh

AU - Taghdiri, Maryam

AU - Papari, Elaheh

AU - Soltani Banavandi, Mohammad Javad

AU - Akbari, Saeide

AU - Tonekaboni, Seyed Hassan

AU - Dehghani, Hossein

AU - Ebrahimpour, Mohammad Reza

AU - Bader, Ingrid

AU - Davarnia, Behzad

AU - Cohen, Monika

AU - Khodaei, Hossein

AU - Albrecht, Beate

AU - Azimi, Sarah

AU - Zirn, Birgit

AU - Bastami, Milad

AU - Wieczorek, Dagmar

AU - Bahrami, Gholamreza

AU - Keleman, Krystyna

AU - Vahid, Leila Nouri

AU - Tzschach, Andreas

AU - Gärtner, Jutta

AU - Gillessen-Kaesbach, Gabriele

AU - Varaghchi, Jamileh Rezazadeh

AU - Timmermann, Bernd

AU - Pourfatemi, Fatemeh

AU - Jankhah, Aria

AU - Chen, Wei

AU - Nikuei, Pooneh

AU - Kalscheuer, Vera M.

AU - Oladnabi, Morteza

AU - Wienker, Thomas F.

AU - Ropers, Hans Hilger

AU - Najmabadi, Hossein

PY - 2019/7/1

Y1 - 2019/7/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85040038397

U2 - 10.1038/s41380-017-0012-2

DO - 10.1038/s41380-017-0012-2

M3 - Journal articles

C2 - 29302074

AN - SCOPUS:85040038397

SN - 1359-4184

VL - 24

SP - 1027

EP - 1039

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 7

ER -

Genetics of intellectual disability in consanguineous families

Abstract

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