Charcot-Marie-Tooth type X: A novel mutation in the Cx32 gene with central conduction slowing.
Charcot-Marie-Tooth disease (CMT) is characterized by distal muscle weakness and wasting, often resulting in foot deformities and gait disturbances, distal sensory impairment and by more or less typical changes in sural nerve biopsy. CMT type 1 is also characterized by reduced nerve conduction velocities. For these demyelinating subtypes, most frequently a 1.5 Mb tandem duplication in chromosome 17p11.2-12 comprising the gene for the peripheral myelin protein 22 (PMP22) is observed (CMT1A), but point mutations in PMP22 have also rarely been reported. X-linked, dominant CMTX1 disease is the second most common type of these hereditary motor and sensory neuropathies (HMSN). Mutations in the X chromosomal gene Connexin32 (Cx32) synonymous gap junction beta-1 (GJB1) are detectable in most X-linked CMT families. We report a novel missense mutation--Tyr65His--in the first extracelullar domain of the Cx32 gene in a Czech CMTX1 family. The mutation was not detectable in 50 healthy controls. The clinical phenotype in both the male proband and his mother was moderate with pronounced peroneal weakness and foot drop. Nerve conduction velocities were intermediately decreased (31-38 m/s) in both patients and slowing of central acoustic conduction (BAEP) was found in both the son and the mother whereas visual central conduction slowing (VEP) was detectable only in the son.
Seeman
P
P
Department of Child Neurology, Second School of Medicine, Charles University Prague, V úvalu 84, Praha 5, Czech Republic. pavel.seeman@lfmotol.cuni.cz
Mazanec
R
R
Ctvrtecková
M
M
Smilková
D
D
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001767:Blinking / Q000502:physiology; D001933:Brain Stem / Q000503:physiopathology; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D017630:Connexins / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005074:Evoked Potentials, Visual / Q000502:physiology; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D009431:Neural Conduction / Q000502:physiology; D010375:Pedigree; D010525:Peripheral Nerves / Q000503:physiopathology; D012018:Reflex / Q000502:physiology; D014960:X Chromosome / Q000235:genetics*; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D004247:DNA; D000097002:Gap Junction beta-1 Protein