HMSN-1 with focally outfolded myelin is a rare nosological entity, characterized by severe impairment of both motor and sensory functions of the lower limbs, and slowing of motor nerve conduction velocity. Characteristic pathological features are irregular redundant loops and thickenings of the myelin sheaths, and segmental demyelination. This condition is commonly considered to be transmitted with autosomal recessive inheritance; however molecular genetic analysis failed to demonstrate any lesion of the PMP22 and PO genes, or linkage to chromosome 8q13-21.1. Two pedigrees are herein described of this disease: affected members showed clinical and neurophysiological findings consistent with a mild form of HMSN-1. In the former, inheritance was autosomal dominant. Sural nerve biopsy of the proband showed decreased density of the myelinated fibres, de/remyelination and rare onion bulbs; several fibres had outfolded myelin. Nucleotide sequencing of the coding region of PO gene revealed the heterozygous TCG→TTG change leading to a leucine for serine substitution at aminoacid position 78, in the extracellular domain of the protein. In the second pedigree, inheritance was dominant, without evidence of male-to-male transmission. Nerve biopsy was performed in two patients, which showed more pronounced Schwann cell hypertrophy than in the previous case. Nucleotide sequencing failed to reveal any alterations of PO coding region. These findings indicate that HMSN-1 with focally folded myelin is a heterogenous polyneuropathy which also includes autosomal dominant forms with variable clinical expression. Myelin outfolding is probably related to specific alterations of myelin related genes.
|Number of pages||1|
|Journal||Italian Journal of Neurological Sciences|
|Publication status||Published - 1997|
ASJC Scopus subject areas
- Clinical Neurology