Charcot‐Marie‐Tooth Neuropathy Type 2 and P0 Point Mutations: Two Novel Amino Acid Substitutions (Asp61Gly; Tyr119Cys) and a Possible “Hotspot” on Thr124Met

Brain Pathology - Tập 10 Số 2 - Trang 235-248 - 2000
Jan Senderek1, B Hermanns1, Ute Lehmann1, Carsten Bergmann1, Gerda Martha Marx2, Christian Kabus3, Vincent Timmerman4, Gisela Stoltenburg‐Didinger5, Johann Michael Schröder1
1Institut für Neuropathologie, Universitätsklinikum der Rheinisch-Westfälischen Technischen Hochschule Aachen, Germany
2Neurologische Abteilung, Diakonie Krankenhaus, Schwäbisch Hall, Germany
3Neurologische Abteilung, Jüdisches Krankenhaus, Berlin, Germany
4Flanders Interuniversity Institute for Biotechnology, Born-Bunge Foundation, University of Antwerp, Department of Biochemistry, Antwerpen, Belgium
5Institut für Neuropathologie, Freie Universität Berlin, Klinikum Benjamin Franklin, Berlin, Germany

Tóm tắt

Mutations in the gene for the major protein component of peripheral nerve myelin, myelin protein zero (MPZ, P0), cause hereditary disorders of Schwann cell myelin such as Charcot‐Marie‐Tooth neuropathy type 1B (CMT1B), Dejerine‐Sottas syndrome (DSS), and congenital hypomyelinating neu‐ropathy (CHN). More recently, P0 mutations were identified in the axonal type of CMT neuropathy, CMT2, which is different from the demyelinating variants with respect to electroneurography and nerve pathology. We screened 49 patients with a clinical and histopathological diagnosis of CMT2 for mutations in the P0 gene. Three heterozygous single nucleotide changes were detected: two novel mis‐sense mutations, Asp61Gly and Tyr119Cys, and the known Thr124Met substitution, that has already been reported in several CMT patients from different European countries. Haplotype analysis for the P0 locus proved that our patients with the 124Met allele were not related to a cohort of patients with the same mutation, all of Belgian descent and all found to share a common ancestor (7).Our data suggest that P0 mutations account for a detectable proportion of CMT2 cases with virtually every patient harbouring a different mutation but recurrence of the Thr124Met amino acid substitution.The high frequency of this peculiar genotype in the European CMT population is presumably not only due to a founder effect but Thr124Met might constitute a mutation hotspot in the P0 gene as well.

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Tài liệu tham khảo

10.1002/jnr.490250119

10.1006/geno.1993.1334

10.1126/science.8266101

10.1086/302542

10.1136/jnnp.66.6.779

Cooper DN, 1993, Human gene mutation

10.1093/brain/122.2.281

Ding Y, 1994, The cytoplasmic domain of myelin glycoprotein P0 interacts with the negatively charged phospholipid bilayers, J Biol Chem, 269, 10764, 10.1016/S0021-9258(17)34125-X

10.1016/0896-6273(90)90057-M

Dyck PJ, 1993, Peripheral neuropathy, 1094

10.1002/ana.410350515

10.1212/WNL.47.3.761

10.1111/j.1750-3639.1993.tb00739.x

10.1093/brain/103.2.259

Hayasaka K, 1993, Charcot‐Marie‐Tooth neuropathy type 1B is associated with mutations of the myelin P0 gene, Nature Genet, 5, 31, 10.1038/ng0993-31

10.1038/ng1193-266

10.1016/S0006-291X(05)81094-0

10.1093/hmg/5.9.1373

10.1212/WNL.42.4.903

Kwon JM, 1995, Assignment of a second Charcot‐Marie‐Tooth type II locus to chromosome 3q, Am J Hum Genet, 57, 853

10.1002/glia.440070402

10.1016/0092-8674(85)90198-9

10.1016/0896-6273(88)90211-5

10.1016/0092-8674(91)90613-4

10.1212/WNL.50.5.1397

10.1007/BF00206959

10.1159/000472166

10.1212/WNL.52.5.1106-f

10.1093/hmg/2.12.2051

10.1016/0960-8966(91)90055-W

10.1016/0959-4388(93)90139-P

10.1038/ng1193-269

10.1002/(SICI)1098-1004(1996)7:1<36::AID-HUMU5>3.0.CO;2-N

10.1016/0736-5748(88)90025-1

10.1002/(SICI)1098-1004(1997)10:6<443::AID-HUMU5>3.0.CO;2-E

10.1212/WNL.37.9.1460

Sakamoto Y, 1987, Complete amino acid sequence of P0 protein in bovine peripheral nerve myelin, J Biol Chem, 262, 4208, 10.1016/S0021-9258(18)61334-1

10.1002/(SICI)1097-4598(199802)21:2<217::AID-MUS9>3.0.CO;2-E

10.1002/humu.1380110170

Schröder JM, 1999, Pathologie peripherer Nerven, 10.1007/978-3-642-58426-8

10.1016/S0022-510X(99)00146-X

10.1016/S0896-6273(00)80176-2

10.1007/s004390050522

10.1016/S0960-8966(99)00008-5

10.1111/j.1399-0004.1974.tb00638.x

10.1016/S0022-510X(97)00202-5

10.1212/WNL.52.9.1827

10.1212/WNL.46.5.1311

10.1038/ng1292-288

10.1016/S0896-6273(00)80177-4

10.1038/ng0498-382

Wolf C, 1997, Screening of myelin genes in CMT1 patients without duplication in chromosomal region 17p11.2‐p12 [abstract], J Periph Nerv Sys, 2, 402

10.1016/0888-7543(91)90370-T

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Brain Pathology

Tập 10 Số 2

235-248

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