Maroofian, R;
Riemersma, M;
Jae, LT;
Zhianabed, N;
Willemsen, MH;
Wissink-Lindhout, WM;
Willemsen, MA;
de Brouwer, APM;
Mehrjardi, MYV;
Ashrafi, MR;
et al.
Maroofian, R; Riemersma, M; Jae, LT; Zhianabed, N; Willemsen, MH; Wissink-Lindhout, WM; Willemsen, MA; de Brouwer, APM; Mehrjardi, MYV; Ashrafi, MR; Kusters, B; Kleefstra, T; Jamshidi, Y; Nasseri, M; Pfundt, R; Brummelkamp, TR; Abbaszadegan, MR; Lefeber, DJ; van Bokhoven, H
(2017)
B3GALNT2 mutations associated with non-syndromic autosomal recessive intellectual disability reveal a lack of genotype-phenotype associations in the muscular dystrophy-dystroglycanopathies.
Genome Med, 9 (1).
p. 118.
ISSN 1756-994X
https://doi.org/10.1186/s13073-017-0505-2
SGUL Authors: Jamshidi, Yalda
Abstract
BACKGROUND: The phenotypic severity of congenital muscular dystrophy-dystroglycanopathy (MDDG) syndromes associated with aberrant glycosylation of α-dystroglycan ranges from the severe Walker-Warburg syndrome or muscle-eye-brain disease to mild, late-onset, isolated limb-girdle muscular dystrophy without neural involvement. However, muscular dystrophy is invariably found across the spectrum of MDDG patients. METHODS: Using linkage mapping and whole-exome sequencing in two families with an unexplained neurodevelopmental disorder, we have identified homozygous and compound heterozygous mutations in B3GALNT2. RESULTS: The first family comprises two brothers of Dutch non-consanguineous parents presenting with mild ID and behavioral problems. Immunohistochemical analysis of muscle biopsy revealed no significant aberrations, in line with the absence of a muscular phenotype in the affected siblings. The second family includes five affected individuals from an Iranian consanguineous kindred with mild-to-moderate intellectual disability (ID) and epilepsy without any notable neuroimaging, muscle, or eye abnormalities. Complementation assays of the compound heterozygous mutations identified in the two brothers had a comparable effect on the O-glycosylation of α-dystroglycan as previously reported mutations that are associated with severe muscular phenotypes. CONCLUSIONS: In conclusion, we show that mutations in B3GALNT2 can give rise to a novel MDDG syndrome presentation, characterized by ID associated variably with seizure, but without any apparent muscular involvement. Importantly, B3GALNT2 activity does not fully correlate with the severity of the phenotype as assessed by the complementation assay.
Item Type: |
Article
|
Additional Information: |
© The Author(s). 2017
Open Access
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
Keywords: |
B3GALNT2, Dystroglycan, Epilepsy, Intellectual disability, Muscular dystrophy-dystroglycanopathy syndrome, Dystroglycan, B3GALNT2, Muscular dystrophy-dystroglycanopathy syndrome, Intellectual disability, Epilepsy, 0604 Genetics, 1103 Clinical Sciences |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS) |
Journal or Publication Title: |
Genome Med |
ISSN: |
1756-994X |
Language: |
eng |
Dates: |
Date | Event |
---|
22 December 2017 | Published | 5 December 2017 | Accepted |
|
Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
Project ID | Funder | Funder ID |
---|
W.OR09-15 | Prinses Beatrix Spierfonds | UNSPECIFIED | 241995 | EU FP7 project GENCODYS | UNSPECIFIED | 40-00506-98-9001 | Dutch Organisation for Scientific Research | UNSPECIFIED | 91713359 | Dutch Organisation for Scientific Research | UNSPECIFIED |
|
PubMed ID: |
29273094 |
Web of Science ID: |
WOS:000418664700004 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/109527 |
Publisher's version: |
https://doi.org/10.1186/s13073-017-0505-2 |
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