A new type of hereditary motor and sensory neuropathy linked to chromosome 3

Abstract

We report the clinical, pathological, and genetic findings of 23 patients in 8 families with hereditary motor and sensory neuropathy (proximal dominant form) (HMSN-P) in Okinawa, Japan. The clinical features were unique with respect to autosomal dominant inheritance, Kennedy-Alter-Sung syndrome-like proximal dominant neurogenic atrophy, obvious sensory involvement, painful muscle cramp, fasciculations, areflexia, and high incidences of elevated creatine kinase levels, hyperlipidemia, and diabetes mellitus. Electrophysiological and pathological studies revealed typical motor and sensory axonal neuropathy, and decreased numbers of anterior born and dorsal ganglion cells, which suggested the presence of neuronopathy in HMSN-P. Genetic linkage studies showed a lod score of 4.04 (two-point analysis) in DNA marker D3S1284. Haplotype analysis showed that the gene locus of the disease was mapped to 3p14.1-q13 bracketed by D3S1285 and D3S1281. In this region, the patients' chromosomes showed an obvious increase in the allele frequency of five markers. One allele in D3S1591 was identical in all patients but had a low frequency in the control population. This finding suggested the presence of linkage disequilibrium and a common origin of this allele in all patients with HMSN-P. The HMSN-P described here is a new clinical entity characterized by unique clinical manifestations and a new gene locus.

Autosomal dominant HMSN with proximal involvement: new Brazilian cases

“…The current cases were classified as HMSN-P because they fulfilled all diagnostic criteria published previously 2 . In comparison with Takashima's series, our patients had similar clinical onset (muscle cramps, proximal muscle weakness and dysesthesia of the extremities) at almost same median age (41.25 years).…”

“…Laboratorial abnormalities most commonly include high serum levels of creatine kinase, glucose and lipids. Neuropathologic studies revealed decreased number of anterior horn cells and marked loss of myelinated fibers in posterior funiculus, cauda equine, posterior roots, tibial nerve, and sural nerve, without onion-bulb formations 2 . Its locus was mapped to chromo-some 3q13.1 region, and the underlying gene still remains to be identified [3][4][5] .…”

“…We report a family with a rare form of HMSN, Autosomal Dominant Hereditary Motor Sensory Neuropathy with Proximal Dominant Involvement (HMSN-P). The disease was first described in 1997 by Takashima et al 2 who established diagnostic criteria: slowly progressive proximal dominant muscle weakness and atrophy first manifested after the age of 30 years; family history of autosomal dominant inheritance; fasciculation in the extremities and trunk; absent deep tendon reflexes; and presence of abnormalities in sensory nerve conduction. Needle electromyography frequently displays fasciculation and fibrillation potentials.…”

Μοριακή γενετική μελέτη της κληρονομικής πολυνευροπάθειας Charcot - Marie - Tooth (CMT)

“… HMSN-P έχει χαρτογραφηθεί στο χρωμόσωμα 3q13.1 (Takashima et al 1997) αλλά το υπεύθυνο γονίδιο παραμένει ακόμα άγνωστο.…”

“…Οι κινητικές ταχύτητες αγωγής νεύρων είναι φυσιολογικές ή ελαφρώς μειωμένες (33-57 m/s). (Takashima et al 1997) unknown Επικρατητικός φυλοσύνδετος τύπος στο χρωμόσωμα X CMTX1 Xq13.1 #302800 (Gal et al 1985) GJB1 *304040 (Bergoffen et al 1993)…”