HMSN-P: Refinement of a locus for autosomal dominant hereditary motor and sensor

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J Hum Genet. 2007;52(11):907-14.

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, Jambaldorj 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.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17906970 [PubMed - indexed for MEDLINE]

nt 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, Jambaldorj 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.