Whole genome sequencing identifies a duplicated region encompassing Xq13.2q13.3 in a large Iranian family with intellectual disability
Abstract Background The X chromosome has historically been one of the most thoroughly investigated chromosomes regarding intellectual disability (ID), whose etiology is attributed to many factors including copy number variations (CNVs). Duplications of the long arm of the X chromosome have been repo...
Main Authors: | , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2020-10-01
|
Series: | Molecular Genetics & Genomic Medicine |
Subjects: | |
Online Access: | https://doi.org/10.1002/mgg3.1418 |
id |
doaj-1cdd4c65b15846df92f9152a83a6f484 |
---|---|
record_format |
Article |
spelling |
doaj-1cdd4c65b15846df92f9152a83a6f4842020-11-25T03:44:37ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-10-01810n/an/a10.1002/mgg3.1418Whole genome sequencing identifies a duplicated region encompassing Xq13.2q13.3 in a large Iranian family with intellectual disabilitySepideh Mehvari0Farzaneh Larti1Hao Hu2Zohreh Fattahi3Maryam Beheshtian4Seyedeh Sedigheh Abedini5Sanaz Arzhangi6Hans‐Hilger Ropers7Vera M. Kalscheuer8Daniel Auld9Kimia Kahrizi10Yasser Riazalhosseini11Hossein Najmabadi12Genetics Research Center University of Social Welfare and Rehabilitation Sciences Tehran IranGenetics Research Center University of Social Welfare and Rehabilitation Sciences Tehran IranMax Planck Institute for Molecular Genetics Berlin GermanyGenetics Research Center University of Social Welfare and Rehabilitation Sciences Tehran IranGenetics Research Center University of Social Welfare and Rehabilitation Sciences Tehran IranGenetics Research Center University of Social Welfare and Rehabilitation Sciences Tehran IranGenetics Research Center University of Social Welfare and Rehabilitation Sciences Tehran IranMax Planck Institute for Molecular Genetics Berlin GermanyMax Planck Institute for Molecular Genetics Berlin GermanyDepartment of Human Genetics McGill University Montreal Quebec CanadaGenetics Research Center University of Social Welfare and Rehabilitation Sciences Tehran IranDepartment of Human Genetics McGill University Montreal Quebec CanadaGenetics Research Center University of Social Welfare and Rehabilitation Sciences Tehran IranAbstract Background The X chromosome has historically been one of the most thoroughly investigated chromosomes regarding intellectual disability (ID), whose etiology is attributed to many factors including copy number variations (CNVs). Duplications of the long arm of the X chromosome have been reported in patients with ID, short stature, facial anomalies, and in many cases hypoplastic genitalia and/or behavioral abnormalities. Methods Here, we report on a large Iranian family with X‐linked ID caused by a duplication on the X chromosome identified by whole genome sequencing in combination with linkage analysis. Results Seven affected males in different branches of the family presented with ID, short stature, seizures, facial anomalies, behavioral abnormalities (aggressiveness, self‐injury, anxiety, impaired social interactions, and shyness), speech impairment, and micropenis. The duplication of the region Xq13.2q13.3, which is ~1.8 Mb in size, includes seven protein‐coding OMIM genes. Three of these genes, namely SLC16A2, RLIM, and NEXMIF, if impaired, can lead to syndromes presenting with ID. Of note, this duplicated region was located within a linkage interval with a LOD score >3. Conclusion Our report indicates that CNVs should be considered in multi‐affected families where no candidate gene defect has been identified in sequencing data analysis.https://doi.org/10.1002/mgg3.1418intellectual disabilitywhole genome sequencingXq duplicationXq13.2q13.3 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sepideh Mehvari Farzaneh Larti Hao Hu Zohreh Fattahi Maryam Beheshtian Seyedeh Sedigheh Abedini Sanaz Arzhangi Hans‐Hilger Ropers Vera M. Kalscheuer Daniel Auld Kimia Kahrizi Yasser Riazalhosseini Hossein Najmabadi |
spellingShingle |
Sepideh Mehvari Farzaneh Larti Hao Hu Zohreh Fattahi Maryam Beheshtian Seyedeh Sedigheh Abedini Sanaz Arzhangi Hans‐Hilger Ropers Vera M. Kalscheuer Daniel Auld Kimia Kahrizi Yasser Riazalhosseini Hossein Najmabadi Whole genome sequencing identifies a duplicated region encompassing Xq13.2q13.3 in a large Iranian family with intellectual disability Molecular Genetics & Genomic Medicine intellectual disability whole genome sequencing Xq duplication Xq13.2q13.3 |
author_facet |
Sepideh Mehvari Farzaneh Larti Hao Hu Zohreh Fattahi Maryam Beheshtian Seyedeh Sedigheh Abedini Sanaz Arzhangi Hans‐Hilger Ropers Vera M. Kalscheuer Daniel Auld Kimia Kahrizi Yasser Riazalhosseini Hossein Najmabadi |
author_sort |
Sepideh Mehvari |
title |
Whole genome sequencing identifies a duplicated region encompassing Xq13.2q13.3 in a large Iranian family with intellectual disability |
title_short |
Whole genome sequencing identifies a duplicated region encompassing Xq13.2q13.3 in a large Iranian family with intellectual disability |
title_full |
Whole genome sequencing identifies a duplicated region encompassing Xq13.2q13.3 in a large Iranian family with intellectual disability |
title_fullStr |
Whole genome sequencing identifies a duplicated region encompassing Xq13.2q13.3 in a large Iranian family with intellectual disability |
title_full_unstemmed |
Whole genome sequencing identifies a duplicated region encompassing Xq13.2q13.3 in a large Iranian family with intellectual disability |
title_sort |
whole genome sequencing identifies a duplicated region encompassing xq13.2q13.3 in a large iranian family with intellectual disability |
publisher |
Wiley |
series |
Molecular Genetics & Genomic Medicine |
issn |
2324-9269 |
publishDate |
2020-10-01 |
description |
Abstract Background The X chromosome has historically been one of the most thoroughly investigated chromosomes regarding intellectual disability (ID), whose etiology is attributed to many factors including copy number variations (CNVs). Duplications of the long arm of the X chromosome have been reported in patients with ID, short stature, facial anomalies, and in many cases hypoplastic genitalia and/or behavioral abnormalities. Methods Here, we report on a large Iranian family with X‐linked ID caused by a duplication on the X chromosome identified by whole genome sequencing in combination with linkage analysis. Results Seven affected males in different branches of the family presented with ID, short stature, seizures, facial anomalies, behavioral abnormalities (aggressiveness, self‐injury, anxiety, impaired social interactions, and shyness), speech impairment, and micropenis. The duplication of the region Xq13.2q13.3, which is ~1.8 Mb in size, includes seven protein‐coding OMIM genes. Three of these genes, namely SLC16A2, RLIM, and NEXMIF, if impaired, can lead to syndromes presenting with ID. Of note, this duplicated region was located within a linkage interval with a LOD score >3. Conclusion Our report indicates that CNVs should be considered in multi‐affected families where no candidate gene defect has been identified in sequencing data analysis. |
topic |
intellectual disability whole genome sequencing Xq duplication Xq13.2q13.3 |
url |
https://doi.org/10.1002/mgg3.1418 |
work_keys_str_mv |
AT sepidehmehvari wholegenomesequencingidentifiesaduplicatedregionencompassingxq132q133inalargeiranianfamilywithintellectualdisability AT farzanehlarti wholegenomesequencingidentifiesaduplicatedregionencompassingxq132q133inalargeiranianfamilywithintellectualdisability AT haohu wholegenomesequencingidentifiesaduplicatedregionencompassingxq132q133inalargeiranianfamilywithintellectualdisability AT zohrehfattahi wholegenomesequencingidentifiesaduplicatedregionencompassingxq132q133inalargeiranianfamilywithintellectualdisability AT maryambeheshtian wholegenomesequencingidentifiesaduplicatedregionencompassingxq132q133inalargeiranianfamilywithintellectualdisability AT seyedehsedighehabedini wholegenomesequencingidentifiesaduplicatedregionencompassingxq132q133inalargeiranianfamilywithintellectualdisability AT sanazarzhangi wholegenomesequencingidentifiesaduplicatedregionencompassingxq132q133inalargeiranianfamilywithintellectualdisability AT hanshilgerropers wholegenomesequencingidentifiesaduplicatedregionencompassingxq132q133inalargeiranianfamilywithintellectualdisability AT veramkalscheuer wholegenomesequencingidentifiesaduplicatedregionencompassingxq132q133inalargeiranianfamilywithintellectualdisability AT danielauld wholegenomesequencingidentifiesaduplicatedregionencompassingxq132q133inalargeiranianfamilywithintellectualdisability AT kimiakahrizi wholegenomesequencingidentifiesaduplicatedregionencompassingxq132q133inalargeiranianfamilywithintellectualdisability AT yasserriazalhosseini wholegenomesequencingidentifiesaduplicatedregionencompassingxq132q133inalargeiranianfamilywithintellectualdisability AT hosseinnajmabadi wholegenomesequencingidentifiesaduplicatedregionencompassingxq132q133inalargeiranianfamilywithintellectualdisability |
_version_ |
1724513728432439296 |