Refinement of a locus for autosomal dominant hereditary motor and sensory neurop

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J Hum Genet. 2007 Oct 2

Refinement of a locus for autosomal dominant hereditary motor and

sensory neuropathy with proximal dominancy (HMSN-P) and genetic

heterogeneity.

Maeda K, Kaji R, Yasuno K, Jambal

dorj J, Nodera H, Takashima H, Nakagawa M, Makino S, Tamiya G.

Department of Neurology and Neuroscience, Tokushima University

Graduate School of Medicine, Tokushima, 770-8503, Japan.

Hereditary motor and sensory neuropathy with proximal dominancy

(HMSN-P) is an adult-onset peripheral neurodegenerative disorder

which has been reported only in the Okinawa Islands, Japan. The

disease locus of " Okinawa-type " HMSN-P has been previously mapped to

3q13.1, with all affected individuals sharing an identical haplotype

around the locus, suggesting that the undiscovered causative

mutation in HMSN-P originated from a single founder.

We have newly found two large families from the western part of

Japan within which multiple members developed symptoms similar to

those exhibited by HMSN-P patients from Okinawa, with no record of

affinal connection between the islands.

Using these pedigrees with " Kansai-type " HMSN-P, we carried out a

linkage study utilizing eight microsatellite markers and identified

a candidate region on 3q13.1 cosegregating with the disease (maximum

two-point LOD score of 8.44 at theta = 0.0) overlapping with the

Okinawa-type HMSN-P locus.

However, the disease haplotype shared among all affected members in

these families was different from that in the Okinawa kindred,

suggesting allelic heterogeneity. Such allelic variation should aid

in the identification of the disease-causative gene. Moreover, the

allelic heterogeneity of HMSN-P in the Japanese population suggests

that HMSN-P may be more common across other ethnic groups, but

classified into other disease categories.