OJGen  Vol.4 No.6 , December 2014
Point Mutation Analysis of PMP22 in Patients Referred for Hereditary Neuropathy with Liability to Pressure Palsies
ABSTRACT
A cohort of 404 patients referred for hereditary neuropathy with liability to pressure palsies was tested initially for the common PMP22 whole gene deletion. 94 whole gene deletions were detected, plus three partial gene deletions, and the remaining 307 patients were screened for PMP22 point mutations. Nine point mutations were identified (8.5% of all mutations), eight of which were in exon 5, suggesting a point mutation hotspot for individuals with this condition. Sequencing analysis of PMP22 exon 5 should therefore be included as a routine diagnostic test for gene deletion-negative patients.

Cite this paper
Brown, S. and Bunyan, D. (2014) Point Mutation Analysis of PMP22 in Patients Referred for Hereditary Neuropathy with Liability to Pressure Palsies. Open Journal of Genetics, 4, 426-433. doi: 10.4236/ojgen.2014.46040.
References
[1]   De Jong, J.G.Y. (1947) Over families met hereditarie disposite tot het optreten van neuritiden, gecorreleard met migraine. Psychiatrische en Neurologische Bladenuitgegeven, 50, 60-76.

[2]   Lewis, R.A., Sumner, A.J. and Shy, M.E. (2000) Electrophysiological Features of Inherited Demyelinating Neuropathies: A Reappraisal in the Era of Molecular Diagnosis. Muscle and Nerve, 23, 1472-1487.
http://dx.doi.org/10.1002/1097-4598(200010)23:10<1472::AID-MUS3>3.0.CO;2-#

[3]   Li, J., Krajewski, K., Shy, M.E. and Lewis, R.A. (2002) Hereditary Neuropathy with Liability to Pressure Palsy: The Electrophysiology Fits the Name. Neurology, 58, 1769-1773.
http://dx.doi.org/10.1212/WNL.58.12.1769

[4]   Davies, D.M. (1954) Recurrent Peripheral-Nerve Palsies in a Family. The Lancet, 254, 266-268.
http://dx.doi.org/10.1016/S0140-6736(54)90193-2

[5]   Gabreels-Festen, A.A.W.M., Gabreels, F.J.M., Joosten, E.M.G., Vingerhoets, H.M. and Renier, W.O. (1992) Hereditary Neuropathy with Liability to Pressure Palsies in Childhood. Neuropediatrics, 23, 138-143.
http://dx.doi.org/10.1055/s-2008-1071329

[6]   Potocki, L., Chen, K.S., Koeuth, T., Killian, J., Iannaccone, S.T., Shapira, S.K., et al. (1999) DNA Rearrangements on Both Homologues of Chromosome 17 in a Mildly Delayed Individual with a Family History of Autosomal Dominant Carpal Tunnel Syndrome. American Journal of Human Genetics, 64, 471-478.
http://dx.doi.org/10.1086/302240

[7]   Chance, P.F., Alderson, M.K., Leppig, K.A., Lensch, M.W., Matsunami, N., Smith, B., et al. (1993) DNA Deletion Associated with Hereditary Neuropathy with Liability to Pressure Palsies. Cell, 72, 143-151.
http://dx.doi.org/10.1016/0092-8674(93)90058-X

[8]   Mariman, E.C.M., Gabreels-Festen, A.A.W.M., van Beersum, S.E.C., Valentijn, L.J., Baas, F., Bolhuis, P.A., et al. (1993) Gene for Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) Maps to Chromosome 17 at or Close to the Locus for HMSN Type 1. Human Genetics, 92, 87-90.
http://dx.doi.org/10.1007/BF00216152

[9]   Le Guern, E., Sturtz, F., Gugenheim, M., Gouider, R., Bonnebouche, C., Ravise, N., et al. (1994) Detection of Deletion within 17p11.2 in 7 French Families with Hereditary Neuropathy with Liability to Pressure Palsies (HNPP). Cytogenetics and Cell Genetics, 65, 261-264.
http://dx.doi.org/10.1159/000133643

[10]   Mariman, E.C.M., Gabreels-Festen, A.A.W.M., van Beersum, S.E.C., Valentijn, L.J., Baas, F., Bolhuis, P.A., et al. (1994) Prevalence of the 1.5-Mb 17p Deletion in Families with Hereditary Neuropathy with Liability to Pressure Palsies. Annals of Neurology, 36, 650-655.
http://dx.doi.org/10.1002/ana.410360415

[11]   Silander, K., Halonen, P., Sara, R., Kalimo, H., Falck, B., Savontaus, M.L. (1994) DNA Analysis in Finnish Patients with Hereditary Neuropathy with Liability to Pressure Palsies (HNPP). Journal of Neurology, Neurosurgery and Psychiatry, 57, 1260-1262.
http://dx.doi.org/10.1136/jnnp.57.10.1260

[12]   Umehara, F., Kiwaki, T., Yoshikawa, H., Nishimura, T., Nakagawa, M., Matsumoto, W., et al. (1995) Deletion in Chromosome 17p11.2 including the Peripheral Myelin Protein-22 (PMP-22) Gene in Hereditary Neuropathy with Liability to Pressure Palsies. Journal of Neurological Sciences, 133, 173-176.
http://dx.doi.org/10.1016/0022-510X(95)00188-8

[13]   Gonnaud, P.M., Sturtz, F., Fourbil, Y., Bonnebouche, C., Tranchant, C., Warter, J.M., et al. (1995) DNA Analysis as a Tool to Confirm the Diagnosis of Asymptomatic Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) with Further Evidence for the Occurrence of de Novo Mutations. Acta Neurologica Scandinavica, 92, 313-318.
http://dx.doi.org/10.1111/j.1600-0404.1995.tb00135.x

[14]   Kleopa, K.A., Georgiou, D.M., Nicolaou, P., Koutsou, P., Papathanasiou, E., Kyriakides, T., et al. (2004) A Novel PMP22 Mutation ser22phe in a Family with Hereditary Neuropathy with Liability to Pressure Palsies and CMT1A Phenotypes. Neurogenetics, 5, 171-175.
http://dx.doi.org/10.1007/s10048-004-0184-1

[15]   Snipes, G.J., Suter, U., Welcher, A.A. and Shooter, E.M. (1992) Characterization of a Novel Peripheral Nervous System Myelin Protein (PMP-22/SR13). Journal of Cell Biology, 117, 225-238.
http://dx.doi.org/10.1083/jcb.117.1.225

[16]   Li, J., Ghandour, K., Radovanovic, D., Shy, R.R., Krajewski, K.M., Shy, M.E., et al. (2007) Stoichiometric Alteration of PMP22 Protein Determines the Phenotype of Hereditary Neuropathy with Liability to Pressure Palsies. Archives of Neurology, 64, 974-978.
http://dx.doi.org/10.1001/archneur.64.7.974

[17]   Muglia, M., Patitucci, A., Rizzi, R., Ungaro, C., Conforti, F.L., Gabriele, A.L., et al. (2007) A Novel Point Mutation in PMP22 Gene in an Italian Family with Hereditary Neuropathy with Liability to Pressure Palsies. Journal of Neurological Sciences, 263, 194-197.
http://dx.doi.org/10.1016/j.jns.2007.05.034

[18]   Nicholson, G.A., Valentijn, L.J., Cherryson, A.K., Kennerson, M.L., Bragg, T.L., DeKroon, R.M., et al. (1994) A Frame Shift Mutation in the PMP22 Gene in Hereditary Neuropathy with Liability to Pressure Palsies. Nature Genetics, 6, 263-266.
http://dx.doi.org/10.1038/ng0394-263

[19]   Zhang, F., Khajavi, M., Connolly, A.M., Towne, C.F., Batish, S.D. and Lupski, J.R. (2009) The DNA Replication FoSTeS/MMBIR Mechanism Can Generate Genomic, Genic and Exonic Complex Rearrangements in Humans. Nature Genetics, 41, 849-853.
http://dx.doi.org/10.1038/ng.399

[20]   Bort, S., Nelis, E., Timmerman, V., Sevilla, T., Cruz-Martinez, A., Martinez, F., et al. (1997) Mutational Analysis of the MPZ, PMP22 and Cx32 Genes in Patients of Spanish Ancestry with Charcot-Marie-Tooth Disease and Hereditary Neuropathy with Liability to Pressure Palsies. Human Genetics, 99, 746-754.
http://dx.doi.org/10.1007/s004390050442

[21]   Brozková, D., Mazanec, R., Rychly, Z., Haberlová, J., Böhm, J., Staněk, J., et al. (2011) Four Novel Point Mutations in the PMP22 Gene with Phenotypes of HNPP and Dejerine-Sottas Neuropathy. Muscle and Nerve, 44, 819-822.
http://dx.doi.org/10.1002/mus.22189

[22]   Sahenk, Z., Chen, L. and Freimer, M. (1998) A Novel PMP22 Point Mutation Causing HNPP Phenotype: Studies on Nerve Xenografts. Neurology, 5, 702-707.
http://dx.doi.org/10.1212/WNL.51.3.702

[23]   Bellone, E., Balestra, P., Ribizzi, G., Schenone, A., Zocchi, G., Di Maria, E., et al. (2006) An Abnormal mRNA Produced by a Novel PMP22 Splice Site Mutation Associated with HNPP. Journal of Neurology, Neurosurgery and Psychiatry, 77, 538-540.
http://dx.doi.org/10.1136/jnnp.2005.075242

[24]   Meuleman, J., Pou-Serradell, A., Lofgren, A., Ceuterick, C., Martin, J.J., Timmerman, V., et al. (2001) A Novel 3’-Splice Site Mutation in Peripheral Myelin Protein 22 Causing Hereditary Neuropathy with Liability to Pressure Palsies. Neuromuscular Disorders, 11, 400-403.
http://dx.doi.org/10.1016/S0960-8966(00)00214-5

[25]   Haites, N.E., Nelis, E. and Van Broeckhoven, C. (1998) 3rd Workshop of the European CMT Consortium: 54th ENMC International Workshop on Genotype/Phenotype Correlations in Charcot-Marie-Tooth Type 1 and Hereditary Neuropathy with Liability to Pressure Palsies, 28-30 November 1997, Naarden, The Netherlands. Neuromuscular Disorders, 8, 591-603.
http://dx.doi.org/10.1016/S0960-8966(98)00067-4

[26]   Nelis, E., Haites, N. and Van Broeckhoven, C. (1999) Mutations in the Peripheral Myelin Genes and Associated Genes in Inherited Peripheral Neuropathies. Human Mutation, 13, 11-28.
http://dx.doi.org/10.1002/(SICI)1098-1004(1999)13:1<11::AID-HUMU2>3.0.CO;2-A

[27]   Nodera, H., Nishimura, M., Logigian, E.L., Herrmann, D.N. and Kaji, R. (2003) HNPP Due to a Novel Missense Mutation of the PMP22 Gene. Neurology, 60, 1863-1864.
http://dx.doi.org/10.1212/01.WNL.0000066049.13848.F2

[28]   Luigetti, M., Conte, A., Madia, F., Mereu, M.L., Zollino, M., Marangi, G., et al. (2008) A New Single-Nucleotide Deletion of PMP22 in an HNPP Family without Recurrent Palsies. Muscle and Nerve, 38, 1060-1064.
http://dx.doi.org/10.1002/mus.21083

[29]   Young, P., Wiebusch, H., Stogbauer, F., Ringelstein, B., Assmann, G. and Funke, H. (1997) A Novel Frameshift Mutation in PMP22 Accounts for Hereditary Neuropathy with Liability to Pressure Palsies. Neurology, 48, 450-452.
http://dx.doi.org/10.1212/WNL.48.2.450

[30]   Lenssen, P.P., Gabreëls-Festen, A.A., Valentijn, L.J., Jongen, P.J., van Beersum, S.E., van Engelen, B.G., et al. (1998) Hereditary Neuropathy with Liability to Pressure Palsies. Phenotypic Differences between Patients with the Common Deletion and a PMP22 Frame Shift Mutation. Brain, 121, 1451-1458.
http://dx.doi.org/10.1093/brain/121.8.1451

[31]   Yurrebaso, I., Casado, O.L., Barcena, J., de Nanclares, G.P. and Aguirre, U. (2014) Clinical, Electrophysiological and Magnetic Resonance Findings in a Family with Hereditary Neuropathy with Liability to Pressure Palsies Caused by a Novel PMP22 Mutation. Neuromuscular Disorders, 24, 56-62.
http://dx.doi.org/10.1016/j.nmd.2013.09.005

[32]   Moszyńska, I., Kabzińska, D., Sinkiewicz-Darol, E. and Kochański, A. (2009) A Newly Identified Thr99fsX110 Mutation in the PMP22 Gene Associated with an Atypical Phenotype of the Hereditary Neuropathy with Liability to Pressure Palsies. Acta Biochimica Polonica, 56, 627-630.

[33]   Marrosu, M.G., Vaccargiu, S., Marrosu, G., Vannelli, A., Cianchetti, C. and Muntoni, F. (1997) A Novel Point Mutation in the Peripheral Myelin Protein 22 (PMP22) Gene Associated with Charcot-Marie-Tooth Disease Type 1A. Neurology, 48, 489-493.
http://dx.doi.org/10.1212/WNL.48.2.489

[34]   Russo, M., Laurá, M., Polke, J.M., Davis, M.B., Blake, J., Brandner, S., et al. (2011) Variable Phenotypes Are Associated with PMP22 Missense Mutations. Neuromuscular Disorders, 21, 106-114.
http://dx.doi.org/10.1016/j.nmd.2010.11.011

[35]   Shy, M.E., Scavina, M.T., Clark, A., Krajewski, K.M., Li, J., Kamholz, J., et al. (2006) T118M PMP22 Mutation Causes Partial Loss of Function and HNPP-Like Neuropathy. Annals of Neurology, 59, 358-364.
http://dx.doi.org/10.1002/ana.20777

[36]   Bissar-Tadmouri, N., Parman, Y., Boutrand, L., Deymeer, F., Serdaroglu, P., Vandenberghe, A., et al. (2000) Mutational Analysis and Genotype/Phenotype Correlation in Turkish Charcot-Marie-Tooth Type 1 and HNPP Patients. Clinical Genetics, 58, 396-402.
http://dx.doi.org/10.1034/j.1399-0004.2000.580511.x

[37]   Pareyson, D. and Taroni, F. (1996) Deletion of the PMP22 Gene and Hereditary Neuropathy with Liability to Pressure Palsies. Current Opinions in Neurology, 9, 348-354.
http://dx.doi.org/10.1097/00019052-199610000-00006

[38]   Pegoraro, E., Gavassini, B.F., Benedetti, S., Menditto, I., Zara, G., Padoan, R., et al. (2005) Co-Segregation of LMNA and PMP22 Gene Mutations in the Same Family. Neuromuscular Disorders, 15, 858-862.
http://dx.doi.org/10.1016/j.nmd.2005.08.008

[39]   Zéphir, H., Stojkovic, T., Latour, P., Hurtevent, J.F., Blankaert, F. and Vermersch P. (2005) A Family with a Novel Frameshift Mutation in the PMP22 Gene (c.433_434insC) Causing a Phenotype of Hereditary Neuropathy with Liability to Pressure Palsies. Neuromuscular Disorders, 15, 493-497.
http://dx.doi.org/10.1016/j.nmd.2005.04.007

[40]   Taroni, F., Botti, S., Sghirlanzoni, A., Botteon, G., DiDonato, S. and Pareyson, D. (1995) A Nonsense Mutation in the PMP22 Gene in Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) Not Associated with the 17p11.2 Deletion. American Journal of Human Genetics, 57, A229.

[41]   Gess, B., Jeibmann, A., Schirmacher, A., Kleffner, I., Schilling, M. and Young, P. (2011) Report of a Novel Mutation in the PMP22 Gene Causing an Axonal Neuropathy. Muscle and Nerve, 43, 605-609.
http://dx.doi.org/10.1002/mus.21973

[42]   Schouten, J.P., McElgunn, C.J., Waaijer, R., Zwijnenburg, D., Diepvens, F. and Pals, G. (2002) Relative Quantification of 40 Nucleic Acid Sequences by Multiplex Ligation-Dependent Probe Amplification. Nucleic Acids Research, 30, e57.
http://dx.doi.org/10.1093/nar/gnf056

[43]   Ng, P.C. and Henikoff, S. (2001) Predicting Deleterious Amino Acid Substitutions. Genome Research, 11, 863-874.
http://dx.doi.org/10.1101/gr.176601

[44]   Adzhubei, I.A., Schmidt, S., Peshkin, L., Ramensky, V.E., Gerasimova, A., Bork, P., et al. (2010) A Method and Server for Predicting Damaging Missense Mutations. Nature Methods, 7, 248-249.
http://dx.doi.org/10.1038/nmeth0410-248

[45]   Young, P., Stögbauer, F., Eller, B., de Jonghe, P., Löfgren, A., Timmerman, V., et al. (2000) PMP22 Thr118Met Is Not a Clinically Relevant CMT1 Marker. Journal of Neurology, 247, 696-700.
http://dx.doi.org/10.1007/s004150070113

[46]   Parman, Y., Plante-Bordeneuve, V., Guiochon-Mantel, A., Eraksoy, M. and Said, G. (1999) Recessive Inheritance of a New Point Mutation of the PMP22 Gene in Dejerine-Sottas Disease. Annals of Neurology, 45, 518-522.
http://dx.doi.org/10.1002/1531-8249(199904)45:4<518::AID-ANA15>3.0.CO;2-U

[47]   Nelis, E., De Jonghe, P., De Vriendt, E., Patel, P.I., Martin, J.J. and Van Broeckhoven, C. (1998) Mutation Analysis of the Nerve Specific Promoter of the Peripheral Myelin Protein 22 Gene in CMT1 Disease and HNPP. Journal of Medical Genetics, 35, 590-593.
http://dx.doi.org/10.1136/jmg.35.7.590

[48]   Sakakura, M., Hadziselimovic, A., Wang, Z., Schey, K.L. and Sanders, C.R. (2011) Structural Basis for the Trembler-J Phenotype of Charcot-Marie-Tooth Disease. Structure, 19, 1160-1169.
http://dx.doi.org/10.1016/j.str.2011.05.009

 
 
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