The authors describe siblings with progressive external ophthalmoplegia (PEO) due to a novel heterozygous A to G transition at nucleotide 955 of C10Orf2 (Twinkle). The mutation was not identified in parents’ blood, h...The authors describe siblings with progressive external ophthalmoplegia (PEO) due to a novel heterozygous A to G transition at nucleotide 955 of C10Orf2 (Twinkle). The mutation was not identified in parents’ blood, hair follicles, buccal mucosa, or urinary epithelium, indicating germ line mosaicism. One sibling presented with sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO), a phenotype previously associated with the POLG1 gene, highlighting the clinical overlap in autosomal PEO.展开更多
The authors sequenced POLG1, C10ORF2, and ANT1 in 38 sporadic progressive external ophthalmoplegia patients with multiple mitochondrial DNA (mtDNA) deletions. Causative mutations were identified in approximately 10%of...The authors sequenced POLG1, C10ORF2, and ANT1 in 38 sporadic progressive external ophthalmoplegia patients with multiple mitochondrial DNA (mtDNA) deletions. Causative mutations were identified in approximately 10%of cases, with two unrelated individuals harboring a novel premature stop codon mutation (1356T > G). None had a mutation in C10ORF2 or ANT1. In the majority of patients, the primary nuclear genetic defect is likely to affect other unknown genes important for mtDNA maintenance.展开更多
Objective: To determine the minimum prevalence of spinocerebellar ataxia type 17 (SCA17) in the north east of England. Patients and methods: A defined region containing 2,516,500 individuals with 192 families with und...Objective: To determine the minimum prevalence of spinocerebellar ataxia type 17 (SCA17) in the north east of England. Patients and methods: A defined region containing 2,516,500 individuals with 192 families with undiagnosed ataxia, 90 patients with a Huntington’s disease-like phenotype and 292 controls. The number of (CAG/CAA)n repeats in the SCA17/TBP gene was determined by fluorescent PCR and sequenced in affected individuals. Results: The mean repeat size for 584 control alleles was 34 (S.D. = 3.58), ranging from 25 to 40. Two index cases had larger alleles with repeat lengths greater than the control range. Affected family members presented in adult life with ataxia followed by extrapyramidal features and cognitive impairment. In one family 44 repeats were associated with a younger age of onset than has been previously described. Conclusions: The minimum prevalence of SCA17 in the north east of England was 0.16/100,000 (upper 95%confidence interval 0.31/100,000).展开更多
文摘The authors describe siblings with progressive external ophthalmoplegia (PEO) due to a novel heterozygous A to G transition at nucleotide 955 of C10Orf2 (Twinkle). The mutation was not identified in parents’ blood, hair follicles, buccal mucosa, or urinary epithelium, indicating germ line mosaicism. One sibling presented with sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO), a phenotype previously associated with the POLG1 gene, highlighting the clinical overlap in autosomal PEO.
文摘The authors sequenced POLG1, C10ORF2, and ANT1 in 38 sporadic progressive external ophthalmoplegia patients with multiple mitochondrial DNA (mtDNA) deletions. Causative mutations were identified in approximately 10%of cases, with two unrelated individuals harboring a novel premature stop codon mutation (1356T > G). None had a mutation in C10ORF2 or ANT1. In the majority of patients, the primary nuclear genetic defect is likely to affect other unknown genes important for mtDNA maintenance.
文摘Objective: To determine the minimum prevalence of spinocerebellar ataxia type 17 (SCA17) in the north east of England. Patients and methods: A defined region containing 2,516,500 individuals with 192 families with undiagnosed ataxia, 90 patients with a Huntington’s disease-like phenotype and 292 controls. The number of (CAG/CAA)n repeats in the SCA17/TBP gene was determined by fluorescent PCR and sequenced in affected individuals. Results: The mean repeat size for 584 control alleles was 34 (S.D. = 3.58), ranging from 25 to 40. Two index cases had larger alleles with repeat lengths greater than the control range. Affected family members presented in adult life with ataxia followed by extrapyramidal features and cognitive impairment. In one family 44 repeats were associated with a younger age of onset than has been previously described. Conclusions: The minimum prevalence of SCA17 in the north east of England was 0.16/100,000 (upper 95%confidence interval 0.31/100,000).
