Leigh syndrome: clinical features and biochemical and DNA abnormalities

Annals of Neurology
S RahmanD R Thorburn

Abstract

We investigated the etiology of Leigh syndrome in 67 Australian cases from 56 pedigrees, 35 with a firm diagnosis and 32 with some atypical features. Biochemical or DNA defects were determined in both groups, ie, 80% in the tightly defined group and 41% in the "Leigh-like" group. Eleven patients had mitochondrial DNA point mutations (nucleotide [nt] 8993 T to G, nt 8993 T to C, or nt 8344 A to G) and 1 Leigh-like patient had a heteroplasmic deletion. Twenty-nine patients had enzyme defects, ie, 13 respiratory chain complex I, 9 complex IV, and 7 pyruvate dehydrogenase complex (PDHC). Complex I deficiency is more common than recognized previously. Six PDHC-deficient patients had mutations in the X-chromosomal gene encoding the E1alpha subunit of PDHC. Parental consanguinity suggested autosomal recessive inheritance in two complex IV-deficient sibships. We found no strong correlation between the clinical features and basic defects. An assumption of autosomal recessive inheritance (frequently made in the past) would have been wrong in nearly one-half (11 of 28 tightly defined and 18 of 41 total patients) of those in whom a cause was found. A specific defect must be identified if reliable genetic counseling is to be provided.

References

Jul 15, 1992·Biochemical and Biophysical Research Communications·T BourgeronP Rustin
Oct 1, 1992·Annals of Neurology·R SakutaI Nonaka
Aug 17, 1991·Lancet·A J Robinson, G A Richardson
Apr 1, 1990·Journal of Child Neurology·P J Grattan-SmithK J Collins
Jan 1, 1989·Journal of Inherited Metabolic Disease·K HayasakaB Kadenbach
Jan 1, 1987·Clinical Neurology and Neurosurgery·P M van ErvenW Ruitenbeek
Oct 1, 1986·The Biochemical Journal·C A WickingG K Brown
Jan 1, 1982·Human Genetics·P J BenkeA E Feuer
Apr 9, 1981·Nature·S AndersonI G Young
Jul 1, 1994·Clinica Chimica Acta; International Journal of Clinical Chemistry·P RustinA Munnich
Mar 1, 1993·The Journal of Pediatrics·E CiafaloniS DiMauro
Apr 17, 1993·Lancet·I R Starkey
Oct 1, 1993·Journal of Paediatrics and Child Health·S A Morris, M G Harbord
Dec 1, 1993·Annals of Neurology·F M SantorelliS DiMauro
Sep 1, 1993·Annals of Neurology·D D de VriesB A van Oost
Aug 1, 1951·Journal of Neurology, Neurosurgery, and Psychiatry·D LEIGH

❮ Previous
Next ❯

Citations

Jan 23, 1999·Annals of Neurology·M S van der KnaapR A Chalmers
Mar 26, 1999·Movement Disorders : Official Journal of the Movement Disorder Society·S FruchtC H Waters
Jul 1, 1996·Annals of Neurology·S DiMauro, D C De Vivo
Nov 24, 1999·Biochemical and Biophysical Research Communications·M J CoenenJ A Smeitink
Jul 14, 2006·Journal of Inherited Metabolic Disease·Rolf J R J JanssenJan A M Smeitink
Jan 29, 2010·Journal of Inherited Metabolic Disease·Saskia KoeneJan A M Smeitink
Dec 12, 2012·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Russell P Saneto, Margret M Sedensky
Mar 22, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Amy C GoldsteinJodie M Vento
Aug 21, 2013·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Yan-Yan MaLi-Ping Zou
Sep 17, 2002·Molecular Aspects of Medicine·Takahiro Yano
Sep 17, 2002·Molecular Aspects of Medicine·Vitaliy B Borisov
Jan 28, 2003·Trends in Genetics : TIG·Patrick F Chinnery
May 30, 2001·Advanced Drug Delivery Reviews·T Pulkes, M G Hanna
Feb 22, 2001·Pediatric Neurology·M J AbsalonK J Mack
Nov 27, 1998·Pediatric Neurology·Y SuzukiS Saitoh
Dec 4, 2001·Neuromuscular Disorders : NMD·Motohiro AkagiShintaro Okada
Sep 1, 1999·The International Journal of Biochemistry & Cell Biology·P E HartzogB D Cain
Jun 23, 2001·Biochimica Et Biophysica Acta·I VanhorebeekP E Declercq
Aug 27, 2005·Mitochondrion·S M S BuddeJ A M Smeitink
Sep 15, 2011·The Journal of Laryngology and Otology·A SudoS Saitoh
Mar 3, 2011·European Journal of Human Genetics : EJHG·Helen SwalwellDavid R Thorburn
Jan 20, 2012·European Journal of Human Genetics : EJHG·Elizna M van der WaltFrancois H van der Westhuizen
Jun 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Albert QuintanaRichard D Palmiter
Jan 17, 2013·Antioxidants & Redox Signaling·Josephine M ForbesMelinda T Coughlan
Jan 10, 2002·The EMBO Journal·Antoni BarrientosAlexander Tzagoloff
May 10, 2008·Journal of Tropical Pediatrics·S Narasimha RaoGiriraj Ratan Chandak
Sep 9, 2005·Journal of Neuro-ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society·Anat KeslerYair Morad
Feb 9, 2000·The Journal of Small Animal Practice·J J WakshlagA J Reynolds

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.