Anticipation of autosomal dominant progressive external ophthalmoplegia with hypogonadism

Muscle & Nerve
A MelbergE Holme

Abstract

A large Swedish family with members affected by progressive external ophthalmoplegia with hypogonadism were followed-up and reviewed. Hypogonadism included delayed sexual maturation, primary amenorrhea, early menopause, and testicular atrophy. Cataracts, cerebellar ataxia, neuropathy, hypoacusia, pes cavus, tremor, parkinsonism, depression, and mental retardation were other features observed in this family. Muscle biopsy samples of advanced cases showed ragged-red fibers, focal cytochrome c oxidase deficiency, and multiple mtDNA deletions by Southern blot analysis. An autosomal dominant mode of inheritance was evident with anticipation in successive generations. Linkage analysis excluded the chromosome 10q23.3-q24.3 region reported as being linked to the disease in a Finnish family with autosomal dominant progressive external ophthalmoplegia. We report for the first time clinical evidence for anticipation in a family with autosomal dominant progressive external ophthalmoplegia. We hypothesize that the nuclear gene causing this enigmatic disorder may be directly influenced by an expansion of an unstable DNA sequence and that the resulting phenotype is caused by a concerted action with multiple deletions of mtDNA.

References

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Citations

Apr 30, 1998·The Japanese Journal of Human Genetics·S DiMauro, K Tanji
Dec 11, 1999·Muscle & Nerve·T H VuE Bonilla
Aug 13, 2011·Current Opinion in Ophthalmology·Anya A Trumler
Dec 30, 2014·Annals of Clinical and Translational Neurology·Satoshi FukeTadafumi Kato
Oct 2, 2001·American Journal of Medical Genetics·A Suomalainen, J Kaukonen
Jan 26, 2016·Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society·Manuel NistalMiguel Reyes-Múgica
Dec 15, 2011·Journal of the Neurological Sciences·Eino J H PalinAnu Suomalainen

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