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Periaxin mutations cause a broad spectrum of demyelinating neuropathies
Author(s) -
Takashima Hiroshi,
Boerkoel Cornelius F.,
De Jonghe Peter,
Ceuterick Chantal,
Martin JeanJacques,
Voit Thomas,
Schröder J.Michael,
Williams Anna,
Brophy Peter J.,
Timmerman Vincent,
Lupski James R.
Publication year - 2002
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10213
Subject(s) - hereditary motor and sensory neuropathy , neuropathology , myelin , mutation , pathology , peripheral myelin protein 22 , medicine , axon , sensory loss , genetics , biology , neuroscience , disease , gene , central nervous system
Previous studies have demonstrated that apparent loss‐of‐function mutations in the periaxin gene cause autosomal recessive Dejerine‐Sottas neuropathy or severe demyelinating Charcot‐Marie‐Tooth disease. In this report, we extend the associated phenotypes with the identification of two additional families with novel periaxin gene mutations (C715X and R82fsX96) and provide detailed neuropathology. Each patient had marked sensory involvement; two siblings with a homozygous C715X mutation had much worse sensory impairment than motor impairment. Despite early disease onset, these siblings with the C715X mutation had relatively slow disease progression and adult motor impairment typical of classic demyelinating Charcot‐Marie‐Tooth neuropathy. In contrast, a patient with the homozygous R82fsX96 mutation had a disease course consistent with Dejerine‐Sottas neuropathy. The neuropathology of patients in both families was remarkable for demyelination, onion bulb and occasional tomacula formation with focal myelin thickening, abnormalities of the paranodal myelin loops, and focal absence of paranodal septate‐like junctions between the terminal loops and axon. Our study indicates a prominent sensory neuropathy resulting from periaxin gene mutations and suggests a role for the carboxyl terminal domain of the periaxin protein.

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