NARP-MILS syndrome caused by 8993 T > G mitochondrial DNA mutation: a clinical, genetic and neuropathological study

• DOI: 10.1007/s00401-006-0040-5
• Publication Date: 2006-03-08T13:22:20Z
• Authors: A. Rojo; Y. Campos; J. M. Sánchez; I. Bonaventura; M. Aguilar; A. García; L. González; M. J. Rey; J. Arenas; M. Olivé; I. Ferrer
• Keywords: Adenosine Triphosphatases; Male; Neurons; 0301 basic medicine; Brain; Peripheral Nervous System Diseases; Syndrome; Middle Aged; DNA, Mitochondrial; Magnetic Resonance Imaging; Pedigree; 3. Good health; 03 medical and health sciences; Phenotype; Cerebellar Diseases; Mutation; Humans; Ataxia; Atrophy; Leigh Disease; Muscle, Skeletal; Tomography, X-Ray Computed; Retinitis Pigmentosa

The 8993 T>G mutation in mitochondrial DNA has been associated with variable syndromes of differing severity ranging from maternally inherited Leigh's syndrome (MILS) to neuropathy, ataxia, retinitis pigmentosa (NARP), depending on the mutation loads in affected patients. We report a kindred with several members in the same generation suffering NARP or Leigh's syndrome due to a 8993 T>G mutation. Post-mortem studies of the brain in one affected member clinically presenting with a neurological disorder intermediate between adult Leigh's syndrome and NARP showed symmetrical lesions of the basal ganglia and brainstem closely resembling those usually described in typical Leigh's syndrome. Analysis of mtDNA in different tissues showed a high proportion of mutant genome in brainstem, cerebral cortex, putamen, cerebellum and thalamus. These observations illustrate the continuum of clinical and neuropathological manifestations associated with the 8993 T>G mutation of the mtDNA.