Clinicopathological and genetic study of early-onset demyelinating neuropathy.
Autosomal recessive demyelinating Charcot-Marie-Tooth disease (CMT4), Dejerine-Sottas disease and congenital hypomyelinating neuropathy are variants of hereditary demyelinating neuropathy of infancy, a genetically heterogeneous group of disorders. To explore the spectrum of early-onset demyelinating neuropathies further, we studied the clinicopathological and genetic aspects of 20 patients born to unaffected parents. In 19 families out of 20, consanguinity between the parents or presence of an affected sib suggested autosomal recessive transmission. Screening of various genes known to be involved in CMT4 revealed six mutations of which five are novel. Four of these novel mutations occurred in the homozygous state and include: one in GDAP1, one in MTMR2, one in PRX and one in KIAA1985. One patient was heterozygous for a novel MTMR2 mutation and still another was homozygous for the founder mutation, R148X, in NDRG1. All patients tested negative for mutations in EGR2. Histopathological examination of nerve biopsy specimens showed a severe, chronic demyelinating neuropathy, with onion bulb formation, extensive demyelination of isolated fibres and axon loss. We did not discern a specific pattern of histopathology that could be correlated to mutations in a particular gene.
Department of Neurology, Istanbul Medical Faculty, Istanbul University, Millet Cad., Capa, 34390 Istanbul, Turkey. parman@tnn.net
Yesim
Y
Parman
Esra
E
Battaloglu
Ibrahim
I
Baris
Birdal
B
Bilir
Mürüvvet
M
Poyraz
Nisrine
N
Bissar-Tadmouri
Anna
A
Williams
Nadia
N
Ammar
Eva
E
Nelis
Vincent
V
Timmerman
Peter
P
De Jonghe
Ayaz
A
Najafov
Ayaz
A
Necefov
Feza
F
Deymeer
Piraye
P
Serdaroglu
Peter J
PJ
Brophy
G
G
Said
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001483:Base Sequence; D001706:Biopsy; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D013497:Sural Nerve / Q000737:chemistry / Q000648:ultrastructure
D008565:Membrane Proteins; C086745:periaxin; C408986:MTMR2 protein, human; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor