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Distal hereditary motor neuropathy (DHMN): a new locus for an autosomal recessive form
Author(s) -
Mostacciuolo ML,
Crestanello E,
Boaretto F,
Boscolo E,
Liguori M,
Tessarolo D,
Vettori A,
Vazza G
Publication year - 2004
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/j.1085-9489.2004.009209bi.x
Subject(s) - genetics , spinal muscular atrophy , locus (genetics) , smn1 , microsatellite , biology , genetic linkage , consanguinity , hereditary motor and sensory neuropathy , gene , pedigree chart , genetic heterogeneity , phenotype , allele
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.