Clinical and molecular features of an infant patient affected by Leigh Disease associated to m.14459G > A mitochondrial DNA mutation: a case report

Here we report the clinical and molecular features of a 15-month-old female LS patient. Direct sequencing of her muscle-derived mtDNA revealed the presence of two apparently homoplasmic variants: the novel m.14792C > G and the already known m.14459G > A resulting in p.His16Asp change in cytochrome b (MT-CYB) and p.Ala72Val substitution in ND6 subunit, respectively. The m.14459G > A was heteroplasmic in the mother's blood-derived DNA.The m.14459G > A might lead to LS, complicated LS or Leber Optic Hereditary Neuropathy. A comprehensive re-evaluation of previously described 14459G > A-mutated patients does not explain this large clinical heterogeneity.Leigh Syndrome (LS, OMIM 256000) is a subacute necrotizing encephalomyelopathy characterized by bilateral symmetrical necrotic lesions of gray matter nuclei in the basal ganglia, diencephalon, cerebellum or brainstem. The onset is usually in early infancy and patients manifest an heterogeneous set of symptoms, such as regression or psychomotor delay, weakness, hypotonia, truncal ataxia, intention tremor associated with lactic acidosis in the blood, cerebrospinal fluid or urine. The prognosis is poor and, in most cases, patients die before age of 5 years. It is the most frequent cause of inherited mitochondrial disorder in infancy (1:40,000) [1].LS inheritance is complex since patients may present mutations in mitochondrial DNA (mtDNA) or in nuclear genes, which predominantly encode for proteins involved in respiratory chain structure and assembly or in coenzyme Q10 biogenesis [2]. Among maternally inherited forms, most of the mutations lay within genes encoding Complex I (ND1-6) and V (ATP6, ATP8) mitochondrial subunits [3].Here we report the clinical, biochemical and molecular features of a pediatric patient affected by Leigh Syndrome associated with the mitochondrial DNA mutation m.14459G > A within MT-ND6 gene.The proband is a 15-month-old female patient born from healthy nonconsanguineous Italian parents after a regu