Two missense mutations of EGR2 R359W and GJB1 V136A in a Charcot-Marie-Tooth disease family.
ABSTRACT During mutational analysis of Charcot-Marie-Tooth (CMT) causative genes, we identified a CMT family with two missense mutations in different genes. A R359W mutation in EGR2 was shared by the affected daughter (proband) and her father. In addition, she had a V136A mutation in GJB1, which was determined to be a de novo mutation. The daughter with two different gene mutations showed more severe clinical, electrophysiological and histopathological phenotypes than her father who had only the EGR2 mutation. We suggest that these phenotypic differences between the proband and her father may have been caused by an altered effect of the genetic modifier in EGR2, or by the additive effect of the EGR2 and GJB1 mutations.
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ABSTRACT: Charcot-Marie-Tooth disease (CMT) is the most common form of inherited motor and sensory neuropathy. Moreover, CMT is a genetically heterogeneous disorder of the peripheral nervous system, with many genes identified as CMT-causative. CMT has two usual classifications: type 1, the demyelinating form (CMT1); and type 2, the axonal form (CMT2). In addition, patients are classified as CMTX if they have an X-linked inheritance pattern and CMT4 if the inheritance pattern is autosomal recessive. A large amount of new information on the genetic causes of CMT has become available, and mutations causing it have been associated with more than 17 different genes and 25 chromosomal loci. Advances in our understanding of the molecular basis of CMT have revealed an enormous diversity in genetic mechanisms, despite a clinical entity that is relatively uniform in presentation. In addition, recent encouraging studies - shown in CMT1A animal models - concerning the therapeutic effects of certain chemicals have been published; these suggest potential therapies for the most common form of CMT, CMT1A. This review focuses on the inherited motor and sensory neuropathy subgroup for which there has been an explosion of new molecular genetic information over the past decade.Journal of Clinical Neurology 06/2006; 2(2):92-106. · 1.69 Impact Factor