Novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia and multisystem failure.
A Saudi Arabian family presented with adult onset autosomal dominant progressive external ophthalmoplegia (adPEO) complicated by late onset reversible failure of the CNS, respiratory, hepatic, and endocrine systems. Clinical findings were suggestive of mitochondrial dysfunction and multiple mitochondrial DNA deletions were demonstrated on long range and real time polymerase chain reaction assays but not on Southern blotting. The disorder is caused by a novel heterozygous PEO1 mutation predicting a Leu360Gly substitution in the twinkle protein. The peculiar clinical presentation expands the variable phenotype observed in adPEO and Twinkle gene mutations.
Bohlega
S
S
Department of Neurosciences, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. boholega@kfshrc.edu.sa
Van Goethem
G
G
Al Semari
A
A
Löfgren
A
A
Al Hamed
M
M
Van Broeckhoven
C
C
Kambouris
M
M
D000328:Adult; D017668:Age of Onset; D000368:Aged; D019943:Amino Acid Substitution; D004265:DNA Helicases / Q000235:genetics*; D004272:DNA, Mitochondrial; D005190:Family; D005260:Female; D006801:Humans; D008875:Middle Aged; D024101:Mitochondrial Proteins; D009102:Multiple Organ Failure / Q000235:genetics*; D009154:Mutation; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012529:Saudi Arabia; D017384:Sequence Deletion
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D004265:DNA Helicases; C431576:TWNK protein, human