Exome sequencing identifies three novel candidate genes implicated in intellectual disability.
Intellectual disability (ID) is a major health problem mostly with an unknown etiology. Recently exome sequencing of individuals with ID identified novel genes implicated in the disease. Therefore the purpose of the present study was to identify the genetic cause of ID in one syndromic and two non-s...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2014-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4236113?pdf=render |
id |
doaj-5a496dc121a647b3a5b9d8be1fcafe62 |
---|---|
record_format |
Article |
spelling |
doaj-5a496dc121a647b3a5b9d8be1fcafe622020-11-25T02:16:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e11268710.1371/journal.pone.0112687Exome sequencing identifies three novel candidate genes implicated in intellectual disability.Zehra AghaZafar IqbalMaleeha AzamHumaira AyubLisenka E L M VissersChristian GilissenSyeda Hafiza Benish AliMoeen RiazJoris A VeltmanRolph PfundtHans van BokhovenRaheel QamarIntellectual disability (ID) is a major health problem mostly with an unknown etiology. Recently exome sequencing of individuals with ID identified novel genes implicated in the disease. Therefore the purpose of the present study was to identify the genetic cause of ID in one syndromic and two non-syndromic Pakistani families. Whole exome of three ID probands was sequenced. Missense variations in two plausible novel genes implicated in autosomal recessive ID were identified: lysine (K)-specific methyltransferase 2B (KMT2B), zinc finger protein 589 (ZNF589), as well as hedgehog acyltransferase (HHAT) with a de novo mutation with autosomal dominant mode of inheritance. The KMT2B recessive variant is the first report of recessive Kleefstra syndrome-like phenotype. Identification of plausible causative mutations for two recessive and a dominant type of ID, in genes not previously implicated in disease, underscores the large genetic heterogeneity of ID. These results also support the viewpoint that large number of ID genes converge on limited number of common networks i.e. ZNF589 belongs to KRAB-domain zinc-finger proteins previously implicated in ID, HHAT is predicted to affect sonic hedgehog, which is involved in several disorders with ID, KMT2B associated with syndromic ID fits the epigenetic module underlying the Kleefstra syndromic spectrum. The association of these novel genes in three different Pakistani ID families highlights the importance of screening these genes in more families with similar phenotypes from different populations to confirm the involvement of these genes in pathogenesis of ID.http://europepmc.org/articles/PMC4236113?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zehra Agha Zafar Iqbal Maleeha Azam Humaira Ayub Lisenka E L M Vissers Christian Gilissen Syeda Hafiza Benish Ali Moeen Riaz Joris A Veltman Rolph Pfundt Hans van Bokhoven Raheel Qamar |
spellingShingle |
Zehra Agha Zafar Iqbal Maleeha Azam Humaira Ayub Lisenka E L M Vissers Christian Gilissen Syeda Hafiza Benish Ali Moeen Riaz Joris A Veltman Rolph Pfundt Hans van Bokhoven Raheel Qamar Exome sequencing identifies three novel candidate genes implicated in intellectual disability. PLoS ONE |
author_facet |
Zehra Agha Zafar Iqbal Maleeha Azam Humaira Ayub Lisenka E L M Vissers Christian Gilissen Syeda Hafiza Benish Ali Moeen Riaz Joris A Veltman Rolph Pfundt Hans van Bokhoven Raheel Qamar |
author_sort |
Zehra Agha |
title |
Exome sequencing identifies three novel candidate genes implicated in intellectual disability. |
title_short |
Exome sequencing identifies three novel candidate genes implicated in intellectual disability. |
title_full |
Exome sequencing identifies three novel candidate genes implicated in intellectual disability. |
title_fullStr |
Exome sequencing identifies three novel candidate genes implicated in intellectual disability. |
title_full_unstemmed |
Exome sequencing identifies three novel candidate genes implicated in intellectual disability. |
title_sort |
exome sequencing identifies three novel candidate genes implicated in intellectual disability. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
Intellectual disability (ID) is a major health problem mostly with an unknown etiology. Recently exome sequencing of individuals with ID identified novel genes implicated in the disease. Therefore the purpose of the present study was to identify the genetic cause of ID in one syndromic and two non-syndromic Pakistani families. Whole exome of three ID probands was sequenced. Missense variations in two plausible novel genes implicated in autosomal recessive ID were identified: lysine (K)-specific methyltransferase 2B (KMT2B), zinc finger protein 589 (ZNF589), as well as hedgehog acyltransferase (HHAT) with a de novo mutation with autosomal dominant mode of inheritance. The KMT2B recessive variant is the first report of recessive Kleefstra syndrome-like phenotype. Identification of plausible causative mutations for two recessive and a dominant type of ID, in genes not previously implicated in disease, underscores the large genetic heterogeneity of ID. These results also support the viewpoint that large number of ID genes converge on limited number of common networks i.e. ZNF589 belongs to KRAB-domain zinc-finger proteins previously implicated in ID, HHAT is predicted to affect sonic hedgehog, which is involved in several disorders with ID, KMT2B associated with syndromic ID fits the epigenetic module underlying the Kleefstra syndromic spectrum. The association of these novel genes in three different Pakistani ID families highlights the importance of screening these genes in more families with similar phenotypes from different populations to confirm the involvement of these genes in pathogenesis of ID. |
url |
http://europepmc.org/articles/PMC4236113?pdf=render |
work_keys_str_mv |
AT zehraagha exomesequencingidentifiesthreenovelcandidategenesimplicatedinintellectualdisability AT zafariqbal exomesequencingidentifiesthreenovelcandidategenesimplicatedinintellectualdisability AT maleehaazam exomesequencingidentifiesthreenovelcandidategenesimplicatedinintellectualdisability AT humairaayub exomesequencingidentifiesthreenovelcandidategenesimplicatedinintellectualdisability AT lisenkaelmvissers exomesequencingidentifiesthreenovelcandidategenesimplicatedinintellectualdisability AT christiangilissen exomesequencingidentifiesthreenovelcandidategenesimplicatedinintellectualdisability AT syedahafizabenishali exomesequencingidentifiesthreenovelcandidategenesimplicatedinintellectualdisability AT moeenriaz exomesequencingidentifiesthreenovelcandidategenesimplicatedinintellectualdisability AT jorisaveltman exomesequencingidentifiesthreenovelcandidategenesimplicatedinintellectualdisability AT rolphpfundt exomesequencingidentifiesthreenovelcandidategenesimplicatedinintellectualdisability AT hansvanbokhoven exomesequencingidentifiesthreenovelcandidategenesimplicatedinintellectualdisability AT raheelqamar exomesequencingidentifiesthreenovelcandidategenesimplicatedinintellectualdisability |
_version_ |
1724888689657511936 |