Anticipation of autosomal dominant progressive external ophthalmoplegia with hypogonadism.

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.

journal_name

Muscle Nerve

journal_title

Muscle & nerve

authors

Melberg A,Arnell H,Dahl N,Stålberg E,Raininko R,Oldfors A,Bakall B,Lundberg PO,Holme E

doi

10.1002/(SICI)1097-4598(199612)19:12<1561::AID-MUS

subject

Has Abstract

pub_date

1996-12-01 00:00:00

pages

1561-9

issue

12

eissn

0148-639X

issn

1097-4598

pii

10.1002/(SICI)1097-4598(199612)19:12<1561::AID-MUS

journal_volume

19

pub_type

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