MYELIN PROTEIN ZERO GENE MUTATED IN CHARCOT-MARIE-TOOTH TYPE-1B PATIENTS

被引:80
作者
SU, Y
BROOKS, DG
LI, LY
LEPERCQ, J
TROFATTER, JA
RAVETCH, JV
LEBO, RV
机构
[1] UNIV CALIF SAN FRANCISCO,DEPT OBSTET & GYNECOL,U-262,SAN FRANCISCO,CA 94143
[2] UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143
[3] SLOAN KETTERING INST CANC RES,MOLEC BIOL PROGRAM,NEW YORK,NY 10021
[4] MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02114
关键词
D O I
10.1073/pnas.90.22.10856
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Autosomal dominant of Charcot-Marie-Tooth disease (CMT), whose gene is type 1B (CMT1B), has slow nerve conduction with demyelinated Schwann cells. In this study the abundant peripheral myelin protein zero (MPZ) gene, MPZ, was mapped 130 kb centromeric to the Fc receptor immunoglobulin gene cluster in band 1q22, and a major MPZ point mutation was found to cosegregate with CMT1B in one large CMT1B family. The MPZ point mutation in 18 of 18 related CMT1B pedigree 1 patients converts a positively charged lysine in codon % to a negatively charged glutamate. The same MPZ locus cosegregates with the CMT1B disease gene in a second CMT1B family [total multipoint logarithm of odds (lod) = 11.4 at theta = 0.00] with a splice junction mutation. Both mutations occur in MPZ protein regions otherwise conserved identically in human, rat, and cow since these species diverged 100 million years ago. MPZ protein, expressed exclusively in myelinated peripheral nerve Schwann cells, constitutes >50% of myelin protein. These mutations are anticipated to disrupt homophilic MPZ binding and result in CMT1B peripheral nerve demyelination.
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页码:10856 / 10860
页数:5
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