Phenotype-genotype correlations in Leigh syndrome: new insights from a multicentre study of 96 patients

Journal of Medical Genetics
Kalliopi SofouNiklas Darin

Abstract

Leigh syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder. While some genetic defects are associated with well-described phenotypes, phenotype-genotype correlations in Leigh syndrome are not fully explored. We aimed to identify phenotype-genotype correlations in Leigh syndrome in a large cohort of systematically evaluated patients. We studied 96 patients with genetically confirmed Leigh syndrome diagnosed and followed in eight European centres specialising in mitochondrial diseases. We found that ataxia, ophthalmoplegia and cardiomyopathy were more prevalent among patients with mitochondrial DNA defects. Patients with mutations in MT-ND and NDUF genes with complex I deficiency shared common phenotypic features, such as early development of central nervous system disease, followed by high occurrence of cardiac and ocular manifestations. The cerebral cortex was affected in patients with NDUF mutations significantly more often than the rest of the cohort. Patients with the m.8993T>G mutation in MT-ATP6 gene had more severe clinical and radiological manifestations and poorer disease outcome compared with patients with the m.8993T>C mutation. Our study provides new insights into phenotype-genotype corre...Continue Reading

References

Mar 1, 1996·Annals of Neurology·S RahmanD R Thorburn
Jul 29, 1998·Brain : a Journal of Neurology·P T OzandO Dabbagh
Aug 17, 2000·Biochemical and Biophysical Research Communications·S M BuddeJ A Smeitink
Jun 23, 2004·The Journal of Biological Chemistry·Hermann SchäggerUlrich Brandt
Dec 4, 2004·Biochimica Et Biophysica Acta·M BugianiM Zeviani
Apr 29, 2005·Brain : a Journal of Neurology·Mikko KärppäKari Majamaa
Feb 9, 2007·Brain : a Journal of Neurology·Elsebet OstergaardMarianne Schwartz
Aug 1, 2007·American Journal of Medical Genetics. Part a·François-Guillaume DebrayGrant A Mitchell
Feb 29, 2008·Annals of Neurology·Itai BergerOrly Elpeleg
Jun 3, 2008·American Journal of Human Genetics·Saskia J G HoefsLambert P van den Heuvel
Apr 2, 2009·Brain : a Journal of Neurology·Felix DistelmaierJan A M Smeitink
Oct 26, 2010·Journal of Medical Genetics·A S LebreN Boddaert
Sep 14, 2012·Journal of Medical Genetics·Elisa Fassone, Shamima Rahman
Aug 21, 2013·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Yan-Yan MaLi-Ping Zou
Apr 16, 2014·Orphanet Journal of Rare Diseases·Kalliopi SofouNiklas Darin
Nov 25, 2014·The Application of Clinical Genetics·Ilene S Ruhoy, Russell P Saneto
Oct 18, 2015·Journal of Inherited Metabolic Disease·Rosalba CarrozzoElsebet Ostergaard
Oct 28, 2015·Annals of Neurology·Nicole J LakeDavid R Thorburn
Dec 15, 2015·Brain : a Journal of Neurology·Juan Darío Ortigoza-EscobarBelén Pérez-Dueñas
Dec 17, 2015·European Journal of Human Genetics : EJHG·Marie ColletAgnès Rötig
Jan 8, 2016·Pediatric Radiology·Eliana BonfanteRoy F Riascos

❮ Previous
Next ❯

Citations

May 2, 2018·Endocrine Regulations·Daniel DanisDaniela Gasperikova
Dec 18, 2018·Movement Disorders : Official Journal of the Movement Disorder Society·Darius Ebrahimi-FakhariAlexander Münchau
Feb 12, 2020·Neurology. Genetics·Claudia StendelUNKNOWN ATP6 Study Group
May 24, 2020·Annals of Neurology·Cesar A P F AlvesGiulio Zuccoli
May 12, 2018·Current Opinion in Neurology·Irene H Flønes, Charalampos Tzoulis
Mar 27, 2019·Annals of Clinical and Translational Neurology·Hannah HayhurstYi Shiau Ng
Jul 19, 2020·Practical Neurology·Yi Shiau Ng, Doug M Turnbull
Feb 26, 2021·Journal of Pediatric Endocrinology & Metabolism : JPEM·Melis KoseFerda Özkınay
Jun 20, 2021·Lancet Neurology·Yi Shiau NgDoug M Turnbull
Jul 1, 2021·Computational and Structural Biotechnology Journal·Xingbo YangYaozu Xiang
Aug 31, 2021·Frontiers in Physiology·Ajibola B BakareShilpa Iyer
Dec 9, 2021·Acta Neurologica Scandinavica·Ji-Hoon Na, Young-Mock Lee

❮ Previous
Next ❯

Related Concepts

Related Feeds

Ataxia

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.

Ataxias (MDS)

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.

Ataxias

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on different types of ataxias here.

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.

© 2022 Meta ULC. All rights reserved