Refinement of a locus for autosomal dominant hereditary motor and sensory neuropathy with proximal dominancy (HMSN-P) and genetic heterogeneity.
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.
Maeda
Kouji
K
Department of Neurology and Neuroscience, Tokushima University Graduate School of Medicine, Tokushima, 770-8503, Japan.
Kaji
Ryuji
R
Department of Neurology and Neuroscience, Tokushima University Graduate School of Medicine, Tokushima, 770-8503, Japan.
Yasuno
Katsuhito
K
Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193, Japan.|Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Kawaguchi, Saitama, 332-0012, Japan.
Jambaldorj
Jamiyansuren
J
Department of Neurology and Neuroscience, Tokushima University Graduate School of Medicine, Tokushima, 770-8503, Japan.|Division of Human Molecular Genetics, Department of Neurology and Neuroscience, Tokushima University Graduate School of Medicine, Tokushima, 770-8503, Japan.
Nodera
Hiroyuki
H
Department of Neurology and Neuroscience, Tokushima University Graduate School of Medicine, Tokushima, 770-8503, Japan.
Takashima
Hiroshi
H
Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medicine, Kagoshima, 890-8520, Japan.
Nakagawa
Masanori
M
Department of Neurology and Gerontology, Kyoto Prefectural University Graduate School of Medicine, Kyoto, 602-0841, Japan.
Makino
Satoshi
S
Division of Human Molecular Genetics, Department of Neurology and Neuroscience, Tokushima University Graduate School of Medicine, Tokushima, 770-8503, Japan.
Tamiya
Gen
G
Division of Human Molecular Genetics, Department of Neurology and Neuroscience, Tokushima University Graduate School of Medicine, Tokushima, 770-8503, Japan. gtamiya@genetix-h.com.
D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005799:Genes, Dominant; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006239:Haplotypes; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree
D017931:DNA Primers