Mutation analysis in Charcot-Marie Tooth disease type 1: point mutations in the MPZ gene and the GJB1 gene cause comparable phenotypic heterogeneity

Charcot-Marie-Tooth disease type 1 (CMT1) is a demyelinating peripheral neu ropathy most commonly caused by a DNA duplication on chromosome 17p11.2 inc luding the peripheral myelin protein 22 (PMP22). Point mutations in the mye lin protein zero gene (MPZ) and gap junction protein, beta-1 gene (GJB1) ar e also found in association with CMT1 or the subclass of CMT type X (CMTX), respectively. Recently point mutations in these genes have been found in p atients showing the axonal variant of CMT, CMT type 2 (CMT2). We here descr ibe the clinical and electro-physiological findings caused by two novel and two recently described MPZ mutations and six GJB1 mutations. Different MPZ and GJB1 mutations were associated with different grades of severity in CM T1 and CMTX. The novel MPZ Glu141(st) op mutation was associated with the a xonal CMT2. We conclude that the clinical and electrophysiological heteroge neity among CMT patients carrying point mutations in MPZ and GJB1 is simila r. Thus for clinical purposes CMT1 and CMT2 patients should be screened for mutations in these two genes after duplication on chromosome 17p11.2 has b een excluded as the disease causing mutation.