Not only dominant, not only optic atrophy: expanding the clinical spectrum associated with OPA1 mutations

Orphanet Journal of Rare Diseases
Alessia NascaDaniele Ghezzi

Abstract

Heterozygous mutations in OPA1 are a common cause of autosomal dominant optic atrophy, sometimes associated with extra-ocular manifestations. Few cases harboring compound heterozygous OPA1 mutations have been described manifesting complex neurodegenerative disorders in addition to optic atrophy. We report here three patients: one boy showing an early-onset mitochondrial disorder with hypotonia, ataxia and neuropathy that was severely progressive, leading to early death because of multiorgan failure; two unrelated sporadic girls manifesting a spastic ataxic syndrome associated with peripheral neuropathy and, only in one, optic atrophy. Using a targeted resequencing of 132 genes associated with mitochondrial disorders, in two probands we found compound heterozygous mutations in OPA1: in the first a 5 nucleotide deletion, causing a frameshift and insertion of a premature stop codon (p.Ser64Asnfs*7), and a missense change (p.Ile437Met), which has recently been reported to have clinical impact; in the second, a novel missense change (p.Val988Phe) co-occurred with the p.Ile437Met substitution. In the third patient a homozygous mutation, c.1180G > A (p.Ala394Thr) in OPA1 was detected by a trio-based whole exome sequencing approach. On...Continue Reading

References

Jul 24, 2002·Nucleic Acids Research·Langping HeDouglass M Turnbull
Oct 22, 2005·Annals of Neurology·Patrizia Amati-BonneauPascal Reynier
Dec 26, 2007·Brain : a Journal of Neurology·Patrizia Amati-BonneauValerio Carelli
Dec 6, 2008·PloS One·Dominik SeelowMarkus Schuelke
Apr 1, 2009·Biochemical and Biophysical Research Communications·Teresa RizzaRosalba Carrozzo
Feb 17, 2010·Brain : a Journal of Neurology·P Yu-Wai-ManP F Chinnery
Oct 27, 2010·Genome Research·Ghizlane ElachouriGuy Lenaers
Jun 4, 2011·Molecular Genetics and Metabolism·Christian P SchaafFernando Scaglia
Jul 19, 2013·Journal of Child Neurology·Stéphanie PaquayIsabelle Maystadt
Jun 28, 2014·Brain : a Journal of Neurology·Tobias BonifertMatthis Synofzik
Jul 12, 2014·Brain : a Journal of Neurology·Dominique BonneauPascal Reynier
Jul 16, 2014·Nature Genetics·Viviana CordedduRaoul C Hennekam
Aug 26, 2014·Brain : a Journal of Neurology·Valerio CarelliEnrico Bertini
Mar 13, 2016·Biochimica Et Biophysica Acta·Andrea LegatiMassimo Zeviani
Sep 27, 2016·American Journal of Human Genetics·Antonella SferraEnrico Bertini

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Citations

Jun 4, 2019·Metabolic Brain Disease·Josef Finsterer, Franco Laccone
May 12, 2018·Current Opinion in Neurology·Irene H Flønes, Charalampos Tzoulis
Mar 29, 2020·Annals of Neurology·Leonardo CaporaliFranco Taroni
Apr 12, 2019·Metabolic Brain Disease·Ayelet ZeremTally Lerman-Sagie
Nov 8, 2020·Drugs·Giulia AmoreChiara La Morgia
Dec 20, 2020·Progress in Retinal and Eye Research·Guy LenaersBernd Wissinger
Feb 20, 2018·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Valentina Del DottoClaudia Zanna
Apr 4, 2021·Biology·Govinda SharmaTimothy E Shutt
Apr 23, 2021·Molecular Genetics and Genomics : MGG·Xingyu XuQingjiong Zhang
Jun 29, 2021·Frontiers in Neurology·Valentina Del Dotto, Valerio Carelli
Aug 7, 2021·Scientific Data·Khadidja GuehlouzMarc Ferré
Sep 23, 2021·Scientific Reports·Isabelle MeunierGuy Lenaers

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Methods Mentioned

BETA
GTPase
PCR
electrophoresis
fluorescence microscopy
biopsy
genotyping
exome sequencing

Software Mentioned

dbNSFP
Genome Analysis Toolkit ( GATK
dbNSFP SVM
Annotation Dependent Depletion ( CADD )
SnpEff
CADD

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