Spinal CMT/dHMN research from U of Padua

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Research from J Peripher Nerv Syst. 2004 Jun;9(2):122-123.

Distal hereditary motor neuropathy (DHMN): a new locus for an autosomal

recessive form.

Mostacciuolo M, Crestanello E, Boaretto F, Boscolo E, Liguori M,

Tessarolo D, Vettori A, Vazza G.

Department of Biology, University of Padua.

Distal hereditary motor neuropathy (dHMN), also known as the spinal form

of Charcot-Marie-Tooth (spinal CMT) disease or as distal spinal muscular

atrophy (dSMA), is an exclusively motor disorder of the peripheral

nervous system. Seven different variants of distal HMN have been

clinically identified and 5 loci have so far been mapped, of which two

for the recessive forms (HMN type 3 and type 6). We collected the DNA of

a family in which some cases of HMN have been clinically diagnosed. This

family lives in a small and geographically isolated village of southern

Italy. Due to the presence of a high frequency of inbreeding evident

from several consanguinity loops, an autosomal recessive inheritance has

been postulated and the involvement of a single gene responsible can be

assumed. To exclude possible involvement of genes causing similar

pathological phenotypes, a preliminary mutational screening for the

genes PMP22 and P0, involved in CMT1, and SMN1 gene, responsible for the

SMA, has been carried out: no mutations were found. Furthermore, a

linkage analysis has been made for the HMN 3 and 6, obtaining negative

LOD score values (less than -2). On the bases of such data and

considering the high informativity of this pedigree (simulated max LOD

score = 4.24 at a recombination frequency of 0.0), we performed a

genomewide analysis using 483 fluorescent-labelled microsatellite

markers. Preliminary results allow us to identify a critical region

cosegregating with the disease in the affected subjects on chromosome

11p.

Distal hereditary motor neuropathy (DHMN): a new locus for an autosomal

recessive form.

Mostacciuolo M, Crestanello E, Boaretto F, Boscolo E, Liguori M,

Tessarolo D, Vettori A, Vazza G.

Department of Biology, University of Padua.

Distal hereditary motor neuropathy (dHMN), also known as the spinal form

of Charcot-Marie-Tooth (spinal CMT) disease or as distal spinal muscular

atrophy (dSMA), is an exclusively motor disorder of the peripheral

nervous system. Seven different variants of distal HMN have been

clinically identified and 5 loci have so far been mapped, of which two

for the recessive forms (HMN type 3 and type 6). We collected the DNA of

a family in which some cases of HMN have been clinically diagnosed. This

family lives in a small and geographically isolated village of southern

Italy. Due to the presence of a high frequency of inbreeding evident

from several consanguinity loops, an autosomal recessive inheritance has

been postulated and the involvement of a single gene responsible can be

assumed. To exclude possible involvement of genes causing similar

pathological phenotypes, a preliminary mutational screening for the

genes PMP22 and P0, involved in CMT1, and SMN1 gene, responsible for the

SMA, has been carried out: no mutations were found. Furthermore, a

linkage analysis has been made for the HMN 3 and 6, obtaining negative

LOD score values (less than -2). On the bases of such data and

considering the high informativity of this pedigree (simulated max LOD

score = 4.24 at a recombination frequency of 0.0), we performed a

genomewide analysis using 483 fluorescent-labelled microsatellite

markers. Preliminary results allow us to identify a critical region

cosegregating with the disease in the affected subjects on chromosome

11p.