A novel type of hereditary motor and sensory neuropathy characterized by a mild phenotype.
BACKGROUND
Three loci for autosomal dominant hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth disease type 1 (CMT1) have been identified on chromosomes 17p11.2 (CMT1A), 1q21-q23 (CMT1B), and 10q21.1-q22.1 (designated here as CMT1D). The genes involved are peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ), and the early growth response element 2 (EGR2), respectively. Probably a fourth locus (CMT1C) exists since some autosomal dominant HMSN I families have been excluded for linkage with the CMT1A and CMT1B loci. Four loci for autosomal dominant hereditary motor and sensory neuropathy type II (HMSN II) or Charcot-Marie-Tooth disease type 2 (CMT2) have been localized on chromosomes 1p35-p36 (CMT2A), 3q13-q22 (CMT2B), 7p14 (CMT2D), and 3p (HMSN-P).


OBJECTIVE
To describe the clinical, electrophysiologic, and neuropathological features of a novel type of Charcot-Marie-Tooth disease.


METHODS
We performed linkage studies with anonymous DNA markers flanking the known CMT1 and CMT2 loci. Patients and their relatives underwent clinical neurologic examination and electrophysiologic testing. In the proband, a sural nerve biopsy specimen was examined.


RESULTS
Linkage studies excluded all known CMT1 and CMT2 loci. The clinical phenotype is mild and almost all affected individuals remain asymptomatic. Electrophysiologic and histopathological studies showed signs of a demyelinating neuropathy, but the phenotype is unusual for either autosomal dominant HMSN I or HMSN II.


CONCLUSIONS
Our findings indicate that the HMSN in this family represents a novel clinical and genetic entity.
De Jonghe
P
P
Department of Biochemistry, University Hospital Antwerp, Belgium. dejonghe@uia.ua.ac.be
Timmerman
V
V
Nelis
E
E
De Vriendt
E
E
Löfgren
A
A
Ceuterick
C
C
Martin
J J
JJ
Van Broeckhoven
C
C
D001706:Biopsy; D002607:Charcot-Marie-Tooth Disease / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D002878:Chromosomes, Human, Pair 1; D002893:Chromosomes, Human, Pair 3; D002897:Chromosomes, Human, Pair 7; D004252:DNA Mutational Analysis; D004594:Electrophysiology; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000502:physiology; D008875:Middle Aged; D009185:Myelin Proteins / Q000235:genetics; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009431:Neural Conduction; D010375:Pedigree; D010641:Phenotype; D011401:Promoter Regions, Genetic; D014459:Ulnar Nerve / Q000502:physiology
D005819:Genetic Markers; D009185:Myelin Proteins; C073687:PMP22 protein, human