TY - JOUR T1 - Spinocerebellar ataxia and the A3243G and A8344G mtDNA mutations JF - Journal of Medical Genetics JO - J Med Genet SP - e22 LP - e22 DO - 10.1136/jmg.39.5.e22 VL - 39 IS - 5 AU - P F Chinnery AU - D T Brown AU - K Archibald AU - A Curtis AU - D M Turnbull Y1 - 2002/05/01 UR - http://jmg.bmj.com/content/39/5/e22.abstract N2 - The majority of pedigrees with autosomal dominant cerebellar ataxia (ADCA) harbour a pathological expansion of a trinucleotide repeat at one of five genetic loci: spinocerebellar ataxia (SCA) 1, 2, 3, 6, and 7.1 Other loci have been associated with ADCA in a limited number of families,1–3 but in a significant number of pedigrees the genetic basis remains uncertain. Mitochondrial DNA (mtDNA) defects may present with cerebellar ataxia, with or without corticospinal tract involvement.4 MtDNA rearrangements are usually sporadic and may cause ataxia as part of the Kearns-Sayre syndrome. MtDNA point mutations may also cause a spinocerebellar syndrome that may be transmitted down the maternal line.5, 6 In small pedigrees, it may not be possible to distinguish between maternal and dominant modes of transmission. This raises the possibility that mtDNA point mutations may be responsible for the ataxia seen in some SCA mutation negative families. To test this hypothesis, we identified 29 independent pedigrees with ataxia and an inheritance pattern consistent with mitochondrial transmission and 54 sporadic cases of ataxia. We excluded a pathological trinucleotide expansion at the common SCA loci and then looked for the two most common mtDNA point mutations associated with ataxia, A3243G and A8344G, in a clinically affected subject from each family. Spinocerebellar ataxia cases were prospectively referred to the Northern Genetics Service (UK) over a 15 year period. Genomic DNA was extracted from whole blood, and standard techniques were used to identify subjects with Friedreich's ataxia (FA) and SCA 1, 2, 3, 6, 7, and 8. The remaining cases were divided into three categories by pedigree analysis: (1) independent pedigrees with at least one documented paternal transmission of the ataxia (n=16); (2) independent pedigrees with no paternal transmission but at least one documented maternal transmission (n=29); and (3) sporadic cases of … ER -