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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
New Findings in a Global Approach to Dissect the Whole Phenotype of PLA2G6 Gene Mutations
PLoS ONE, Volume 8, No. 10, Article e76831, Year 2013
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Description
Mutations in PLA2G6 gene have variable phenotypic outcome including infantile neuroaxonal dystrophy, atypical neuroaxonal dystrophy, idiopathic neurodegeneration with brain iron accumulation and Karak syndrome. The cause of this phenotypic variation is so far unknown which impairs both genetic diagnosis and appropriate family counseling. We report detailed clinical, electrophysiological, neuroimaging, histologic, biochemical and genetic characterization of 11 patients, from 6 consanguineous families, who were followed for a period of up to 17 years. Cerebellar atrophy was constant and the earliest feature of the disease preceding brain iron accumulation, leading to the provisional diagnosis of a recessive progressive ataxia in these patients. Ultrastructural characterization of patients' muscle biopsies revealed focal accumulation of granular and membranous material possibly resulting from defective membrane homeostasis caused by disrupted PLA2G6 function. Enzyme studies in one of these muscle biopsies provided evidence for a relatively low mitochondrial content, which is compatible with the structural mitochondrial alterations seen by electron microscopy. Genetic characterization of 11 patients led to the identification of six underlying PLA2G6 gene mutations, five of which are novel. Importantly, by combining clinical and genetic data we have observed that while the phenotype of neurodegeneration associated with PLA2G6 mutations is variable in this cohort of patients belonging to the same ethnic background, it is partially influenced by the genotype, considering the age at onset and the functional disability criteria. Molecular testing for PLA2G6 mutations is, therefore, indicated in childhood-onset ataxia syndromes, if neuroimaging shows cerebellar atrophy with or without evidence of iron accumulation. © 2013 Salih et al.
Authors & Co-Authors
Salih, Mustafa Abdalla M.
Saudi Arabia, Riyadh
College of Medicine
Mundwiller, Emeline
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Khan, Arif Omar
Saudi Arabia, Riyadh
King Khaled Eye Specialist Hospital
AlDrees, Abdulmajeed Abdurrahman
Saudi Arabia, Riyadh
College of Medicine
Elmalik, Salah A.
Saudi Arabia, Riyadh
College of Medicine
Hassan, Hamdy H.
Saudi Arabia, Riyadh
College of Medicine
Al-Owain, Mohammed Abdulaziz
Saudi Arabia, Riyadh
King Faisal Specialist Hospital and Research Centre
Alkhalidi, Hisham Mohammed Said
Saudi Arabia, Riyadh
College of Medicine
Katona, Istvan
Germany, Aachen
Uniklinik Rwth Aachen
Kabiraj, Mohammad Muslim Uddin
Saudi Arabia, Riyadh
Riyadh Military Hospital
Chrast, Roman
Switzerland, Lausanne
Université de Lausanne Unil
Kentab, Amal Y.
Saudi Arabia, Riyadh
College of Medicine
AlZaidan, Hamad Ibrahim
Saudi Arabia, Riyadh
King Faisal Specialist Hospital and Research Centre
Rodenburg, Richard J.T.
Netherlands, Nijmegen
Radboud University Medical Center
Bosley, Thomas M.
Saudi Arabia, Riyadh
College of Medicine
United States, Camden
Cooper University Hospital
Weis, Joachim A.
Germany, Aachen
Uniklinik Rwth Aachen
Kœnig, Michel
France, Strasbourg
Université de Strasbourg
Stévanin, Giovanni
France, Paris
Hôpital Universitaire Pitié Salpêtrière
France, Paris
École Pratique Des Hautes Études
France, Paris
Inserm
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Sorbonne Université
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Azzedine, Hamid
Switzerland, Lausanne
Université de Lausanne Unil
Statistics
Citations: 42
Authors: 19
Affiliations: 15
Identifiers
Doi:
10.1371/journal.pone.0076831
e-ISSN:
19326203
Research Areas
Disability
Genetics And Genomics
Maternal And Child Health
Study Design
Cohort Study