Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions

Chiara La Morgia, Leonardo Caporali, Francesca Gandini, Anna Olivieri, Francesco Toni, Stefania Nassetti, Daniela Brunetto, Carlotta Stipa, Cristina Scaduto, Antonia Parmeggiani, Caterina Tonon, Raffaele Lodi, Antonio Torroni, Valerio Carelli

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have been associated with variably overlapping phenotypes of Leber's hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads also to a Leigh-like phenotype.Case presentation: A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1 mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H background, were also present.Conclusion: This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the primary LHON mutation.

Original languageEnglish
Number of pages5
JournalBMC Neurology
Volume14
Issue number116
DOIs
Publication statusPublished - 28 May 2014
Externally publishedYes

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Leber's Hereditary Optic Atrophy
Optic Nerve Diseases
Mitochondrial DNA
Brain Stem
Mutation
Mitochondrial Encephalomyopathies
Leigh Disease
Vestibular Nuclei
Phenotype
Vertigo
Vomiting
Stroke
Genes

Cite this

La Morgia, Chiara ; Caporali, Leonardo ; Gandini, Francesca ; Olivieri, Anna ; Toni, Francesco ; Nassetti, Stefania ; Brunetto, Daniela ; Stipa, Carlotta ; Scaduto, Cristina ; Parmeggiani, Antonia ; Tonon, Caterina ; Lodi, Raffaele ; Torroni, Antonio ; Carelli, Valerio. / Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions. In: BMC Neurology. 2014 ; Vol. 14, No. 116.
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title = "Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions",
abstract = "Background: An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have been associated with variably overlapping phenotypes of Leber's hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads also to a Leigh-like phenotype.Case presentation: A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1 mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H background, were also present.Conclusion: This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the primary LHON mutation.",
keywords = "Bilateral brainstem lesions, Idebenone, Leigh syndrome, LHON, Mitochondrial disease, mtDNA mutation, Vision loss",
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La Morgia, C, Caporali, L, Gandini, F, Olivieri, A, Toni, F, Nassetti, S, Brunetto, D, Stipa, C, Scaduto, C, Parmeggiani, A, Tonon, C, Lodi, R, Torroni, A & Carelli, V 2014, 'Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions', BMC Neurology, vol. 14, no. 116. https://doi.org/10.1186/1471-2377-14-116

Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions. / La Morgia, Chiara; Caporali, Leonardo; Gandini, Francesca; Olivieri, Anna; Toni, Francesco; Nassetti, Stefania; Brunetto, Daniela; Stipa, Carlotta; Scaduto, Cristina; Parmeggiani, Antonia; Tonon, Caterina; Lodi, Raffaele; Torroni, Antonio; Carelli, Valerio.

In: BMC Neurology, Vol. 14, No. 116, 28.05.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions

AU - La Morgia, Chiara

AU - Caporali, Leonardo

AU - Gandini, Francesca

AU - Olivieri, Anna

AU - Toni, Francesco

AU - Nassetti, Stefania

AU - Brunetto, Daniela

AU - Stipa, Carlotta

AU - Scaduto, Cristina

AU - Parmeggiani, Antonia

AU - Tonon, Caterina

AU - Lodi, Raffaele

AU - Torroni, Antonio

AU - Carelli, Valerio

PY - 2014/5/28

Y1 - 2014/5/28

N2 - Background: An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have been associated with variably overlapping phenotypes of Leber's hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads also to a Leigh-like phenotype.Case presentation: A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1 mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H background, were also present.Conclusion: This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the primary LHON mutation.

AB - Background: An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have been associated with variably overlapping phenotypes of Leber's hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads also to a Leigh-like phenotype.Case presentation: A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1 mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H background, were also present.Conclusion: This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the primary LHON mutation.

KW - Bilateral brainstem lesions

KW - Idebenone

KW - Leigh syndrome

KW - LHON

KW - Mitochondrial disease

KW - mtDNA mutation

KW - Vision loss

UR - http://www.scopus.com/inward/record.url?scp=84902082920&partnerID=8YFLogxK

U2 - 10.1186/1471-2377-14-116

DO - 10.1186/1471-2377-14-116

M3 - Article

VL - 14

JO - BMC Neurology

JF - BMC Neurology

SN - 1471-2377

IS - 116

ER -