New mutations in TK2 gene associated with mitochondrial DNA depletion.

Mitochondrial deoxyribonucleic acid depletion syndromes are autosomal recessive disorders characterized by a reduction of the amount of mitochondrial deoxyribonucleic acid, which impairs the synthesis of respiratory chain complexes. Mutations in the deoxyguanosine kinase and polymerase gamma genes have been identified in hepatocerebral forms, whereas thymidine kinase 2 gene mutations have been found in patients with isolated myopathy, encephalomyopathy, or spinal muscular atrophy. Mutations in the gene encoding the beta subunit of the adenosine diphosphate-forming succinyl-coenzyme A synthetase have also been reported in a family. In this report, the clinical, molecular, morphologic, and biochemical features of five children from two independent families with an infantile encephalomyopathy are characterized. The affected children manifested muscle mitochondrial deoxyribonucleic acid depletion and three novel thymidine kinase 2 gene mutations. They consist of a homozygous substitution resulting in Ala to Val change at the highly conserved position 181 of thymidine kinase in the first family, and two heterozygous substitutions in the second family: a Cys to Trp change at residue 108 and a Leu to Pro change at residue 257 of the enzyme. Common clinical features associated with these TK2 mutations are a normal early developmental phase followed by psychomotor regression, encephalopathy often with epileptic seizures, and myopathy with features of a progressive dystrophic process.

Supratentorial multiple sclerosis lesions affect the blink reflex test.

INTRODUCTION: The Blink Reflex Test (BRT) is a neurophysiological examination used for evaluation of brainstem reflex circuits. MRI is the most precise modality for evaluation of MS lesion anatomy. Our study objective was to investigate how the functional results of the neurophysiological BRT relate to the anatomy of MS lesions in routine MRI studies. METHODS: 65 MS patients underwent the BRT within 2 months of a brain MRI showing demyelinating lesions. RESULTS: The overall sensitivity of the BRT was 90.8%, while in patients with at least one brainstem lesion and no brainstem lesions it was 91.4% and 90%, respectively. DISCUSSION: The presence of brainstem lesions does not significantly affect BRT sensitivity. This points to the influence of supratentorial MS lesions on the BRT. Gender, age, disease duration, type of MS, acuteness of an MS event and whether MS diagnosis was recent or not were not variables affecting the results.

Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia.

One form of familial progressive external ophthalmoplegia with multiple mitochondrial DNA deletions recently has been associated with mutations in POLG1, the gene encoding pol gammaA, the catalytic subunit of mitochondrial DNA polymerase. We screened the POLG1 gene in several PEO families and identified five different heterozygous missense mutations of POLG1 in 10 autosomal dominant families. Recessive mutations were found in three families. Our data show that mutations of POLG1 are the most frequent cause of familial progressive external ophthalmoplegia associated with accumulation of multiple mitochondrial DNA deletions, accounting for approximately 45% of our family cohort.