Open AccessA LRSAM1 mutation links Charcot–Marie–Tooth type 2 to P arkinson's disease
Author(s) -
Aerts Marjolein B.,
Weterman Marian A. J.,
Quadri Marialuisa,
Schelhaas H. Jurgen,
Bloem Bastiaan R.,
Esselink Rianne A.,
Baas Frank,
Bonifati Vincenzo,
Warrenburg Bart P.
Publication year - 2016
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.281
Subject(s) - phenotype , medicine , parkinsonism , ubiquitin ligase , mutation , tooth disease , disease , substantia nigra , clinical phenotype , genetics , central nervous system , bioinformatics , pathology , parkinson's disease , ubiquitin , biology , gene
LRSAM1 mutations have been found in recessive and dominant forms of C harcot– M arie– T ooth disease. Within one generation of the original D utch family in which the dominant LRSAM1 mutation was identified, three of the five affected family members have developed P arkinson's disease between ages 50 and 65 years, many years after neuropathy onset. We speculate that this late‐onset parkinsonism is part of the LRSAM 1 phenotype, thus associating a hitherto peripheral nerve disease with a central nervous system phenotype. How the mutated Lrsam1 protein, which normally has E3 ubiquitin ligase activity and is expressed in the nervous system, impacts on substantia nigra neurons is unclear.