Genotype Phenotype Correlation in CMTX

Wayne State University, Detroit MI

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Dominantly inherited demyelinating neuropathies, known as Charcot-Marie-Tooth disease type 1 (CMT1), are among the most common inherited neurological diseases. CMT1 is caused by mutations in one of several genes that are expressed by myelinating Schwann cells, including PMP22, MPZ, and GJB1. In this grant, we will perform the following: Specific aim 1: To delineate the genotype-phenotype correlations which affect disease severity in CMTX. Specific Aim 2: To test the hypothesis that gain of function mutations in Cx32, identified by an abnormal subcellular localization of the protein, or abnormalities on gap junction by dye transfer, producethe most severe CMTX phenotype. Specific Aim 3: To distinguish between gain of function and loss offunction mechanisms participating in the pathogenesis of CMTX, by generating and comparing Gjbl1knockin mice bearing mutations causing severe neuropathy with Gjb1 null mice.