dc.contributor.author | Ullah, MI | |
dc.contributor.author | Nasir, A | |
dc.contributor.author | Ahmad, A | |
dc.contributor.author | Harlalka, GV | |
dc.contributor.author | Ahmad, W | |
dc.contributor.author | Hassan, MJ | |
dc.contributor.author | Baple, EL | |
dc.contributor.author | Crosby, AH | |
dc.contributor.author | Chioza, BA | |
dc.date.accessioned | 2018-04-19T10:48:37Z | |
dc.date.issued | 2018-02-20 | |
dc.description.abstract | BACKGROUND: L-2-hydroxyglutaric aciduria (L2HGA) is a progressive neurometabolic disease of brain caused by mutations of in L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene. Cardinal clinical features include cerebellar ataxia, epilepsy, neurodevelopmental delay, intellectual disability, and other clinical neurological deficits. CASE PRESENTATION: We describe an index case of the family presented with generalised tonic-clonic seizure, developmental delay, intellectual disability, and ataxia. Initially, the differential diagnosis was difficult to be established and a SNP genome wide scan identified the candidate region on chromosome 14q22.1. DNA sequencing showed a novel homozygous mutation in the candidate gene L2HGDH (NM_024884.2: c.178G > A; p.Gly60Arg). The mutation p.Gly60Arg lies in the highly conserved FAD/NAD(P)-binding domain of this mitochondrial enzyme, predicted to disturb enzymatic function. CONCLUSIONS: The combination of homozygosity mapping and DNA sequencing identified a novel mutation in Pakistani family with variable clinical features. This is second report of a mutation in L2HGDH gene from Pakistan and the largest family with L2HGA reported to date. | en_GB |
dc.description.sponsorship | This research was funded by the Medical Research Council UK (MRC) – grant
G1002279 (AHC). | en_GB |
dc.identifier.citation | Vol. 19: 25 | en_GB |
dc.identifier.doi | 10.1186/s12881-018-0532-x | |
dc.identifier.uri | http://hdl.handle.net/10871/32516 | |
dc.language.iso | en | en_GB |
dc.publisher | BioMed Central | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/29458334 | en_GB |
dc.rights | © The Author(s). 2018 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. | en_GB |
dc.subject | Cerebellar ataxia | en_GB |
dc.subject | Developmental delay | en_GB |
dc.subject | Epilepsy | en_GB |
dc.subject | Intellectual disability | en_GB |
dc.subject | L-2-hydroxyglutaric aciduria | en_GB |
dc.subject | L2HGDH | en_GB |
dc.subject | Mutation | en_GB |
dc.subject | Pakistan | en_GB |
dc.title | Identification of novel L2HGDH mutation in a large consanguineous Pakistani family- a case report | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2018-04-19T10:48:37Z | |
dc.identifier.issn | 1471-2350, | |
exeter.place-of-publication | England | en_GB |
dc.description | This is the final version of the article. Available from the publisher via the DOI in this record. | en_GB |
dc.identifier.journal | BMC Medical Genetics | en_GB |