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

Chiara La Morgia12*, Leonardo Caporali1, Francesca Gandini3, Anna Olivieri3, Francesco Toni4, Stefania Nassetti1, Daniela Brunetto12, Carlotta Stipa12, Cristina Scaduto12, Antonia Parmeggiani12, Caterina Tonon5, Raffaele Lodi5, Antonio Torroni3 and Valerio Carelli12

Author Affiliations

1 UOC Clinica Neurologica, IRCCS Istituto delle Scienze Neurologiche di Bologna, Ospedale Bellaria, Bologna, Italy

2 Unità di Neurologia, Dipartimento di Scienze Biomediche e NeuroMotorie (DIBINEM), Università di Bologna, Bologna, Italy

3 Dipartimento di Biologia e Biotecnologie “L. Spallanzani”, Università di Pavia, Pavia, Italy

4 UOC Neuroradiologia, IRCCS Istituto delle Scienze Neurologiche di Bologna, Ospedale Bellaria, Bologna, Italy

5 Unità di RMN Funzionale, Policlinico S.Orsola-Malpighi, Dipartimento di Scienze Biomediche e NeuroMotorie (DIBINEM), Bologna, Italy

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BMC Neurology 2014, 14:116  doi:10.1186/1471-2377-14-116

Published: 28 May 2014



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.


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.

Mitochondrial disease; Vision loss; Bilateral brainstem lesions; LHON; mtDNA mutation; Leigh syndrome; Idebenone