Novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia and multisystem failure

• Published in: Neuromuscular disorders : NMD Vol. 19; no. 12; pp. 845 - 848
• Main Authors: Bohlega, S, Van Goethem, G, Al Semari, A, Löfgren, A, Al Hamed, M, Van Broeckhoven, C, Kambouris, M
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01-12-2009
• Subjects: adPEO; Adult; Age of Onset; Aged; Amino Acid Substitution; DNA Helicases - genetics; DNA, Mitochondrial; Family; Female; Humans; Middle Aged; Mitochondrial Proteins; mtDNA; Multiple Organ Failure - genetics; Mutation; Neurology; Ophthalmoplegia, Chronic Progressive External - genetics; Pedigree; PEO; PEO1; Phenotype; Saudi Arabia; Sequence Deletion; Twinkle gene; Saudi Arabia; PEO1; Twinkle gene; adPEO; PEO; Mutation; mtDNA
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2009.10.002

Abstract 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.