PMID: 7581383Aug 1, 1995Paper

Maternally inherited hearing loss, ataxia and myoclonus associated with a novel point mutation in mitochondrial tRNASer(UCN) gene

Human Molecular Genetics
V TirantiMassimo Zeviani

Abstract

We report on a new maternally-inherited syndrome characterized by a combination of sensorineural hearing loss, ataxia and myoclonus in a large kindred from Sicily. Hearing loss was the most widespread and sometimes the only symptom found in family members. Sequence analysis of the mitochondrial DNA regions encompassing the tRNA genes revealed the presence of a heteroplasmic insertion at nucleotide position 7472. The insertion adds a seventh cytosine to a six-cytosine run that is part of the mitochondrial tRNASer(UCN) gene. Conformational analysis showed that this mutation is likely to alter the structure of the T psi C loop in the tRNASer(UCN) clover leaf secondary structure. Moreover, the degree of heteroplasmy in blood and muscle was correlated with the clinical phenotype, and homoplasmic mutant hybrids showed decreased complex I activity, low oxygen consumption and high lactic acid output, indicating faulty oxidative phosphorylation. Finally, mutation was absent in 381 unrelated maternal lineages, suggesting specific segregation with the disease. We propose that the C7472 insertion-mutation is pathogenic, and etiologically related to hearing loss and other symptoms that define a novel maternally-inherited clinical entity.

Citations

Jan 1, 1996·Journal of Inherited Metabolic Disease·M ZevianiG Uziel
Apr 23, 2013·Biochemical Genetics·Yu DingPan Xu
Mar 18, 2003·Journal of the Neurological Sciences·Manuel Seijo-MartínezCarmen Navarro
Jan 3, 1997·International Journal of Pediatric Otorhinolaryngology·C StinckensC Cremers
May 30, 2001·Advanced Drug Delivery Reviews·T Pulkes, M G Hanna
Jan 20, 1998·Gene·Z H ShahH T Jacobs
Aug 1, 1996·Current Opinion in Neurobiology·K P Steel, S D Brown
Jun 19, 2001·Neuromuscular Disorders : NMD·Y CamposJ Arenas
Mar 21, 2000·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·J Poulton
Jul 25, 2000·Clinical Genetics·G Van Camp, R J Smith
Apr 30, 2005·Nature Reviews. Genetics·Robert W Taylor, Doug M Turnbull
Jan 3, 2007·Cell Research·Guangqian XingXin Cao
Mar 29, 2013·Molecular Biology of the Cell·Sergio Carilla-LatorreRicardo Escalante
Aug 21, 2003·Human Molecular Genetics·Howard T Jacobs
Aug 13, 2002·The Laryngoscope·Kotaro IshikawaKeiichi Ichimura
Aug 19, 2003·Ear and Hearing·Nathan Fischel-Ghodsian
Dec 1, 1998·Journal of Medical Genetics·S SenecaL de Meirleir
Mar 12, 1999·Annual Review of Medicine·D K Simon, D R Johns
Dec 22, 1999·Clinical Chemistry and Laboratory Medicine : CCLM·M F BauerK D Gerbitz
Aug 24, 2013·International Journal of Molecular Medicine·Valeria GuaranAlessandro Martini
Apr 28, 2012·Mitochondrion·Jing ZhengMin-Xin Guan
Sep 27, 2007·Acta Neurologica Scandinavica·C LindbergA Oldfors
Sep 1, 2004·Biochemical and Biophysical Research Communications·Marina ToompuuHoward T Jacobs
May 10, 2007·Bioscience Reports·F ForliS Berrettini
Nov 9, 2001·Annual Review of Genetics·C PetitJ P Hardelin
Aug 24, 2013·Circulation Journal : Official Journal of the Japanese Circulation Society·Pedro VillarM Esther Gallardo
May 22, 2007·Orvosi hetilap·Eniko SáfrányBéla Melegh
Mar 21, 2015·Nature Reviews. Drug Discovery·Ulrich Müller, Peter G Barr-Gillespie
Nov 22, 2001·Lancet·W M FranzH A Katus

❮ Previous
Next ❯

Related Concepts

Related Feeds

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.

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.

Auditory Perception

Auditory perception is the ability to receive and interpret information attained by the ears. Here is the latest research on factors and underlying mechanisms that influence auditory perception.

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.