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November 17, 1993, Vol 270, No. 19 >
ARTICLE | November 17, 1993

Inherited Primary Peripheral Neuropathies: Title and subTitle BreakMolecular Genetics and Clinical Implications of CMT1A and HNPP FREE

James R. Lupski, MD, PhD; Phillip F. Chance, MD; Carlos A. Garcia, MD
[+] Author Affiliations

Reprint requests to the Institute for Molecular Genetics, Baylor College of Medicine, One Baylor Plaza, Anderson 609E, Houston, TX 77030 (Dr Lupski).


JAMA. 1993;270(19):2326-2330. doi:10.1001/jama.1993.03510190082031
Text Size: A A A
Published online
Article
References

CHARCOT-MARIE-TOOTH disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are autosomal dominant, inherited primary demyelinating peripheral neuropathies that appear to result from reciprocal DNA duplication/deletion, respectively, of a 1.5-megabase (Mb) pair region on chromosome 17p. While inherited DNA rearrangements are present in most CMT1A and HNPP patients, new mutation duplication or deletion can be responsible for sporadic cases of CMT1A or HNPP. This critical 1.5-Mb region is likely to contain multiple genes, but a dosage effect of one gene that encodes a myelin protein of the peripheral nerve (PMP22) appears to play a critical role in the disease phenotype. Moreover, PMP22 point mutations associated with CMT1A have been identified in patients who do not have the CMT1A duplication. The recent elucidation of the molecular mechanisms for CMT1A and HNPP has important clinical implications for the diagnosis, prognosis, genetic counseling, and rational approaches to therapy for

REFERENCES

1 +
Dyck PJ, Thomas PK, Griffin JW, Low PA, Poduslo JF, eds. Peripheral Neuropathy . 3rd ed. Philadelphia, Pa: WB Saunders Co; 1993;.
2 +
Collins FS.  Of needles and haystacks: finding human disease genes by positional cloning. Clin Res . 1992;;39:615-623.
3 +
Suter U, Welcher AA, Snipes GJ.  Progress in the molecular understanding of hereditary peripheral neuropathies reveals new insights into the biology of the peripheral nervous system. Trends Neurosci . 1993;;16:50-56.
4 +
Charcot J-M, Marie P.  Sur une forme particulaiere d'atrophie musculaire progressive souvent familiale debutant par les pied et les jambes et atteignant plus tard les mains. Rev Med . 1886;;6:97-138.
5 +
Lupski JR, Garcia CA, Parry G, Patel PI.  Charcot-Marie-Tooth polyneuropathy syndrome: clinical electrophysiological and genetic aspects.  In: Appel S, ed. Current Neurology . St Louis, Mo: Mosby—Yearbook Co; 1991;:1-25.
6 +
Tooth H. The Peroneal Type of Progressive Muscular Atrophy . London, England: HK Lewis; 1886;.
7 +
Dyck PJ, Lambert EH.  Lower motor primary sensory neuron diseases with peroneal muscular atrophy, I: neurologic, genetic, and electrophysiologic findings in hereditary polyneuropathies. Arch Neurol . 1968;;18:603-618.
8 +
Dyck PJ, Lambert EH.  Lower motor and primary sensory neuron diseases with peroneal muscular atrophy, II: neurologic, genetic, and electrophysiologic findings in various neuronal degenerations. Arch Neurol . 1968;;18:619-625.
9 +
Dyck PJ, Chance PF, Lebo RV, Carney JA.  Hereditary motor and sensory neuropathies.  In: Dyck PJ, Thomas PK, Griffin JW, Low PW, Poduslo JF, eds. Peripheral Neuropathy . 3rd ed. Philadelphia, Pa: WB Saunders Co; 1993;:1094-1136.
10 +
Kaku DA, Parry GJ, Malamut R, Lupski JR, Garcia CA.  Nerve conduction studies in Charcot-Marie-Tooth polyneuropathy associated with a segmental duplication of chromosome 17. Neurology . 1993;;43:1806-1808.
11 +
Garcia CA, Malamut R, Parry G, Lupski JR, Patel PI.  Clinical heterogeneity of HMSN-1 in two pairs of identical twins. Neurology . 1992;;40( (suppl) ):301.
12 +
Kaku DA, Parry GJ, Malamut R, Lupski JR, Garcia CA.  Uniform slowing of conduction velocities in Charcot-Marie-Tooth polyneuropathy type 1. Neurology . In press.
13 +
Lupski JR, Garcia CA.  Molecular genetics and neuropathology of Charcot-Marie-Tooth disease type 1A. Brain Pathol . 1992;;2:337-349.
14 +
Nicholson GA.  Penetrance of hereditary motor and sensory neuropathy Ia mutation: assessment by nerve conduction studies. Neurology . 1991;;41:547-552.
15 +
De Jong JGY.  Over families met hereditaire dispositie tot het optreden van neuritiden gecorreleered met migraine. Psychiatr Neurol Bull . 1947;;50:60-76.
16 +
Davies DM.  Recurrent peripheral nerve palsies in a family. Lancet . 1954;;2:266-268.
17 +
Earl CJ, Fullerton PM, Wakefield GS, Schutta HS.  Hereditary neuropathy, with liability to pressure palsies. Q J Med . 1964;;33:481-498.
18 +
Staal A, De Weerdt CJ, Went LN.  Hereditary compression syndrome of peripheral nerves. Neurology . 1965;;15:1008-1017.
19 +
Dyck PJ, Oviatt KF, Lambert EH.  Intensive evaluation of referred unclassified neuropathies yields improved diagnosis. Ann Neurol . 1981;;10:222-226.
20 +
Behse F, Buchthal F, Carlsen F, Knapplis GG.  Hereditary neuropathy with liability to pressure palsies: electrophysiological and histopathological aspects. Brain . 1972;;95:777-794.
21 +
Bradley WG, Madrid R, Thrush DC, Campbell MJ.  Recurrent brachial plexus neuropathy. Brain . 1975;;98:381-398.
22 +
Madrid R, Bradley WG.  The pathology of neuropathies with focal thickening of the myelin sheath (tomaculous neuropathy): studies on the formation of the abnormal myelin sheath. J Neurol Sci . 1975;; 25:415-418.
23 +
Debruyne J, Dehaene I, Martin JJ.  Hereditary pressure-sensitive neuropathy. J Neurol Sci . 1980;; 47:385-394.
24 +
Skre H.  Genetic and clinical aspects of Charcot-Marie-Tooth disease. Clin Genet . 1974;;6:98-118.
25 +
McKusick VA. Mendelian Inheritance in Man: Catalogs of Autosomal Dominant, Autosomal Recessive, and X-linked Phenotypes . 10th ed. Baltimore, Md: The Johns Hopkins University Press; 1992;.
26 +
Vance JM, Nicholson GA, Yamaoka LH, et al.  Linkage of Charcot-Marie-Tooth neuropathy type la to chromosome 17. Exp Neurol . 1986;;104:186-189.
27 +
Bird TD, Ott J, Gilbert ER.  Evidence for linkage of Charcot-Marie-Tooth neuropathy to the Duffy locus on chromosome number 1. Am J Hum Genet . 1982;;34:388-394.
28 +
Chance PF, Bird TD, O'Connell P, Leppert M, Lipe H, Lalouel J-M.  Genetic linkage heterogeneity in type 1 Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy type I). Am J Hum Genet . 1990;;47:915-925.
29 +
Chance PF, Matsunami N, Lensch MW, Smith BS, Bird TD.  Analysis of the DNA duplication 17p11.2 in Charcot-Marie-Tooth neuropathy type 1 pedigrees: additional evidence for a third autosomal CMT1 locus. Neurology . 1992;;42:2037-2041.
30 +
Hentati A, Lamy C, Melki J, Zuber M, Munnich A, de Recondo J.  Clinical and genetic heterogeneity of Charcot-Marie-Tooth disease. Genomics . 1992;; 12:155-157.
31 +
Timmerman V, Raeymaekers P, Nelis E, et al.  Linkage analysis of distal hereditary motor neuropathy type II (distal HMN II) in a single pedigree. J Neurol Sci . 1992;;109:41-48.
32 +
Ben Othmane K, Middleton LT, Loprest LJ, et al.  Localization of a gene (CMT2A) for autosomal dominant Charcot-Marie-Tooth type 2 to chromosome 1p and evidence for genetic heterogeneity. Genomics . 1993;;17:370-375.
33 +
Chance PF, Alderson MK, Leppig KA, et al.  DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell . 1993;;72: 143-151.
34 +
Lupski JR, Montes de Oca-Luna R, Slaugenhaupt S, et al.  DNA duplication associated with Charcot-Marie-Tooth disease type 1A. Cell . 1991;;66:219-232.
35 +
Raeymaekers P, Timmerman V, Nelis E, et al.  Duplication in chromosome 17p11.2 in Charcot-Marie-Tooth neuropathy type la (CMT1a). Neuromuscul Disord . 1991;;1:93-97.
36 +
Pentao L, Wise CA, Chinault AC, Patel PI, Lupski, JR.  Charcot-Marie-Tooth type 1A duplication appears to arise from recombination at repeat sequences flanking the 1.5 Mb monomer unit. Nature Genet . 1992;;2:292-300.
37 +
Hoogendijk JE, Hensels GW, Gabreels-Festen AAWM, et al.  De novo mutation in hereditary motor and sensory neuropathy type 1. Lancet . 1992;;339: 1081-1082.
38 +
Raeymaekers P, Timmerman V, Nelis E, et al.  Estimation of the size of the chromosome 17p11.2 duplication in Charcot-Marie-Tooth neuropathy type la (CMT1a). J Med Genet . 1992;;29:5-11.
39 +
Bellone E, Mandich P, Mancardi GL, et al.  Charcot-Marie-Tooth (CMT) la duplication at 17p11.2 in Italian families. J Med Genet . 1992;;29:492-493.
40 +
Brice A, Ravise N, Stevanin G, et al.  Duplication within chromosome 17p11.2 in 12 families of French ancestry with Charcot-Marie-Tooth disease type la. J Med Genet . 1992;;29:807-812.
41 +
Hallam PJ, Harding AE, Berciano J, Barker DF, Malcom S.  Duplication of part of chromosome 17 is commonly associated with hereditary motor and sensory neuropathy type I (Charcot-Marie-Tooth disease type 1). Ann Neurol . 1992;;31:570-572.
42 +
MacMillan JC, Upadhyaya M, Harper PS.  Charcot-Marie-Tooth disease la (CMT1a): evidence for trisomy of the region p11.2 of chromosome 17 in South Wales families. J Med Genet . 1992;;29:12-13.
43 +
Lupski JR, Pentao L, Williams LL, Patel PI.  Stable inheritance of the CMT1A DNA duplication in two patients with CMT1 and NF1. Am J Med Genet . 1993;;45:92-96.
44 +
Wise CA, Garcia CA, Davis S, et al.  Molecular analyses of unrelated Charcot-Marie-Tooth disease patients suggest a high frequency of the CMT1A duplication. Am J Hum Genet . 1993;;53:853-863.
45 +
Lupski JR, Wise CA, Kuwano A, et al.  Gene dosage is a mechanism for Charcot-Marie-Tooth disease type 1A. Nature Genet . 1992;;1:29-33.
46 +
Chance PF, Bird TD, Matsunami N, Lensch MW, Brothman AR, Feldman GF.  Trisomy 17p associated with Charcot-Marie-Tooth neuropathy type 1A phenotype: evidence for gene dosage as a mechanism in CMT1A. Neurology . 1992;;42:2295-2299.
47 +
Upadhyaya M, Roberts SH, Farnham J, et al.  Charcot-Marie-Tooth disease type 1A (CMT1A) associated with a maternal duplication of chromosome 17p11.2-12. Hum Genet . 1993;;91:392-395.
48 +
Roa BB, Garcia CA, Wise CA, et al.  Gene dosage as a mechanism for a common autosomal dominant peripheral neuropathy: Charcot-Marie-Tooth disease type 1A.  In: Epstein CJ, ed. Phenotypic Mapping of Down Syndrome and Other Aneuploid Conditions . New York, NY: Wiley-Liss Inc; 1993;:187-205.
49 +
Lupski JR.  An inherited DNA rearrangement and gene dosage effect are responsible for the most common autosomal dominant peripheral neuropathy: Charcot-Marie-Tooth disease type 1A. Clin Res . 1992;; 40:645-652.
50 +
Killian JM, Kloepfer HW.  Homozygous expression of a dominant gene for Charcot-Marie-Tooth neuropathy. Ann Neurol . 1979;;5:515-522.
51 +
Dejerine J, Sottas J.  Sur la nevrite interstitielle, hypertrophique et progressive de l'enface. C R Seances Soc Biol Fil . 1893;;45:63-96.
52 +
Suter U, Welcher AA, Ozcelik T, et al.  The Trembler mouse carries a point mutation in a myelin gene. Nature . 1992;;356:241-244.
53 +
Suter U, Moskow JJ, Welcher AA, et al.  A leucine to proline mutation in the putative first transmembrane domain of the 22-kDa peripheral myelin protein in the Trembler-J mouse. Proc Natl Acad Sci U S A . 1992;;89:4382-4386.
54 +
Patel PI, Roa BB, Welcher AA, et al.  The gene for the peripheral myelin protein PMP-22 is a candidate for Charcot-Marie-Tooth disease type 1A. Nature Genet . 1992;;1:159-165.
55 +
Matsunami N, Smith B, Ballard L, et al.  Peripheral myelin protein-22 gene maps in the duplication in chromosome 17p11.2 associated with Charcot-Marie-Tooth 1A. Nature Genet . 1992;;1:176-179.
56 +
Valentijn LJ, Bolhuis PA, Zorn I, et al.  The peripheral myelin gene PMP-22/GAS-3 is duplicated in Charcot-Marie-Tooth disease type 1A. Nature Genet . 1992;;1:166-170.
57 +
Timmerman V, Nelis E, Van Hul W, et al.  The peripheral myelin protein gene PMP-22 is contained within the Charcot-Marie-Tooth disease type 1A duplication. Nature Genet . 1992;;1:171-175.
58 +
Hayasaka K, Himoro M, Nanao K, et al.  Isolation and sequence determination of cDNA encoding PMP22 (PAS-IISR13/GAS-3) of human peripheral myelin. Biochem Biophys Res Commun . 1992;;186:827-831.
59 +
Roa BB, Garcia CA, Suter U, et al.  Charcot-Marie-Tooth disease type 1A: association with a spontaneous point mutation in the PMP22 gene. N Engl J Med . 1993;;329:96-101.
60 +
Valentijn LJ, Baas F, Wolterman RA, et al.  Identical point mutations of PMP-22 in TremblerJ mouse and Charcot-Marie-Tooth disease type 1A. Nature Genet . 1992;;2:288-291.
61 +
Roa BB, Dyck PJ, Marks HG, Chance PF, Lupski JR.  Dejerine-Sottas syndrome associated with point mutation in the peripheral myelin protein 22 (PMP22) gene. Nature Genet . 1993;;5:269-273.
62 +
Roa BB, Garcia CA, Pentao L, et al.  Evidence for a recessive PMP22 point mutation in Charcot-Marie-Tooth disease type 1A. Nature Genet . 1993;;5:189-194.
63 +
Hayasaka K, Himoro M, Sato W, et al.  Charcot-Marie-Tooth neuropathy type 1B is associated with mutations of the myelin P0 gene. Nature Genet . 1993;;5:31-34.
64 +
Roa BB, Lupski JR.  Molecular basis of Charcot-Marie-Tooth disease type 1A: gene dosage as a novel mechanism for a common autosomal dominant condition. Am J Med Sci . 1991;;306:177-184.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Dyck PJ, Thomas PK, Griffin JW, Low PA, Poduslo JF, eds. Peripheral Neuropathy . 3rd ed. Philadelphia, Pa: WB Saunders Co; 1993;.
2 +
Collins FS.  Of needles and haystacks: finding human disease genes by positional cloning. Clin Res . 1992;;39:615-623.
3 +
Suter U, Welcher AA, Snipes GJ.  Progress in the molecular understanding of hereditary peripheral neuropathies reveals new insights into the biology of the peripheral nervous system. Trends Neurosci . 1993;;16:50-56.
4 +
Charcot J-M, Marie P.  Sur une forme particulaiere d'atrophie musculaire progressive souvent familiale debutant par les pied et les jambes et atteignant plus tard les mains. Rev Med . 1886;;6:97-138.
5 +
Lupski JR, Garcia CA, Parry G, Patel PI.  Charcot-Marie-Tooth polyneuropathy syndrome: clinical electrophysiological and genetic aspects.  In: Appel S, ed. Current Neurology . St Louis, Mo: Mosby—Yearbook Co; 1991;:1-25.
6 +
Tooth H. The Peroneal Type of Progressive Muscular Atrophy . London, England: HK Lewis; 1886;.
7 +
Dyck PJ, Lambert EH.  Lower motor primary sensory neuron diseases with peroneal muscular atrophy, I: neurologic, genetic, and electrophysiologic findings in hereditary polyneuropathies. Arch Neurol . 1968;;18:603-618.
8 +
Dyck PJ, Lambert EH.  Lower motor and primary sensory neuron diseases with peroneal muscular atrophy, II: neurologic, genetic, and electrophysiologic findings in various neuronal degenerations. Arch Neurol . 1968;;18:619-625.
9 +
Dyck PJ, Chance PF, Lebo RV, Carney JA.  Hereditary motor and sensory neuropathies.  In: Dyck PJ, Thomas PK, Griffin JW, Low PW, Poduslo JF, eds. Peripheral Neuropathy . 3rd ed. Philadelphia, Pa: WB Saunders Co; 1993;:1094-1136.
10 +
Kaku DA, Parry GJ, Malamut R, Lupski JR, Garcia CA.  Nerve conduction studies in Charcot-Marie-Tooth polyneuropathy associated with a segmental duplication of chromosome 17. Neurology . 1993;;43:1806-1808.
11 +
Garcia CA, Malamut R, Parry G, Lupski JR, Patel PI.  Clinical heterogeneity of HMSN-1 in two pairs of identical twins. Neurology . 1992;;40( (suppl) ):301.
12 +
Kaku DA, Parry GJ, Malamut R, Lupski JR, Garcia CA.  Uniform slowing of conduction velocities in Charcot-Marie-Tooth polyneuropathy type 1. Neurology . In press.
13 +
Lupski JR, Garcia CA.  Molecular genetics and neuropathology of Charcot-Marie-Tooth disease type 1A. Brain Pathol . 1992;;2:337-349.
14 +
Nicholson GA.  Penetrance of hereditary motor and sensory neuropathy Ia mutation: assessment by nerve conduction studies. Neurology . 1991;;41:547-552.
15 +
De Jong JGY.  Over families met hereditaire dispositie tot het optreden van neuritiden gecorreleered met migraine. Psychiatr Neurol Bull . 1947;;50:60-76.
16 +
Davies DM.  Recurrent peripheral nerve palsies in a family. Lancet . 1954;;2:266-268.
17 +
Earl CJ, Fullerton PM, Wakefield GS, Schutta HS.  Hereditary neuropathy, with liability to pressure palsies. Q J Med . 1964;;33:481-498.
18 +
Staal A, De Weerdt CJ, Went LN.  Hereditary compression syndrome of peripheral nerves. Neurology . 1965;;15:1008-1017.
19 +
Dyck PJ, Oviatt KF, Lambert EH.  Intensive evaluation of referred unclassified neuropathies yields improved diagnosis. Ann Neurol . 1981;;10:222-226.
20 +
Behse F, Buchthal F, Carlsen F, Knapplis GG.  Hereditary neuropathy with liability to pressure palsies: electrophysiological and histopathological aspects. Brain . 1972;;95:777-794.
21 +
Bradley WG, Madrid R, Thrush DC, Campbell MJ.  Recurrent brachial plexus neuropathy. Brain . 1975;;98:381-398.
22 +
Madrid R, Bradley WG.  The pathology of neuropathies with focal thickening of the myelin sheath (tomaculous neuropathy): studies on the formation of the abnormal myelin sheath. J Neurol Sci . 1975;; 25:415-418.
23 +
Debruyne J, Dehaene I, Martin JJ.  Hereditary pressure-sensitive neuropathy. J Neurol Sci . 1980;; 47:385-394.
24 +
Skre H.  Genetic and clinical aspects of Charcot-Marie-Tooth disease. Clin Genet . 1974;;6:98-118.
25 +
McKusick VA. Mendelian Inheritance in Man: Catalogs of Autosomal Dominant, Autosomal Recessive, and X-linked Phenotypes . 10th ed. Baltimore, Md: The Johns Hopkins University Press; 1992;.
26 +
Vance JM, Nicholson GA, Yamaoka LH, et al.  Linkage of Charcot-Marie-Tooth neuropathy type la to chromosome 17. Exp Neurol . 1986;;104:186-189.
27 +
Bird TD, Ott J, Gilbert ER.  Evidence for linkage of Charcot-Marie-Tooth neuropathy to the Duffy locus on chromosome number 1. Am J Hum Genet . 1982;;34:388-394.
28 +
Chance PF, Bird TD, O'Connell P, Leppert M, Lipe H, Lalouel J-M.  Genetic linkage heterogeneity in type 1 Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy type I). Am J Hum Genet . 1990;;47:915-925.
29 +
Chance PF, Matsunami N, Lensch MW, Smith BS, Bird TD.  Analysis of the DNA duplication 17p11.2 in Charcot-Marie-Tooth neuropathy type 1 pedigrees: additional evidence for a third autosomal CMT1 locus. Neurology . 1992;;42:2037-2041.
30 +
Hentati A, Lamy C, Melki J, Zuber M, Munnich A, de Recondo J.  Clinical and genetic heterogeneity of Charcot-Marie-Tooth disease. Genomics . 1992;; 12:155-157.
31 +
Timmerman V, Raeymaekers P, Nelis E, et al.  Linkage analysis of distal hereditary motor neuropathy type II (distal HMN II) in a single pedigree. J Neurol Sci . 1992;;109:41-48.
32 +
Ben Othmane K, Middleton LT, Loprest LJ, et al.  Localization of a gene (CMT2A) for autosomal dominant Charcot-Marie-Tooth type 2 to chromosome 1p and evidence for genetic heterogeneity. Genomics . 1993;;17:370-375.
33 +
Chance PF, Alderson MK, Leppig KA, et al.  DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell . 1993;;72: 143-151.
34 +
Lupski JR, Montes de Oca-Luna R, Slaugenhaupt S, et al.  DNA duplication associated with Charcot-Marie-Tooth disease type 1A. Cell . 1991;;66:219-232.
35 +
Raeymaekers P, Timmerman V, Nelis E, et al.  Duplication in chromosome 17p11.2 in Charcot-Marie-Tooth neuropathy type la (CMT1a). Neuromuscul Disord . 1991;;1:93-97.
36 +
Pentao L, Wise CA, Chinault AC, Patel PI, Lupski, JR.  Charcot-Marie-Tooth type 1A duplication appears to arise from recombination at repeat sequences flanking the 1.5 Mb monomer unit. Nature Genet . 1992;;2:292-300.
37 +
Hoogendijk JE, Hensels GW, Gabreels-Festen AAWM, et al.  De novo mutation in hereditary motor and sensory neuropathy type 1. Lancet . 1992;;339: 1081-1082.
38 +
Raeymaekers P, Timmerman V, Nelis E, et al.  Estimation of the size of the chromosome 17p11.2 duplication in Charcot-Marie-Tooth neuropathy type la (CMT1a). J Med Genet . 1992;;29:5-11.
39 +
Bellone E, Mandich P, Mancardi GL, et al.  Charcot-Marie-Tooth (CMT) la duplication at 17p11.2 in Italian families. J Med Genet . 1992;;29:492-493.
40 +
Brice A, Ravise N, Stevanin G, et al.  Duplication within chromosome 17p11.2 in 12 families of French ancestry with Charcot-Marie-Tooth disease type la. J Med Genet . 1992;;29:807-812.
41 +
Hallam PJ, Harding AE, Berciano J, Barker DF, Malcom S.  Duplication of part of chromosome 17 is commonly associated with hereditary motor and sensory neuropathy type I (Charcot-Marie-Tooth disease type 1). Ann Neurol . 1992;;31:570-572.
42 +
MacMillan JC, Upadhyaya M, Harper PS.  Charcot-Marie-Tooth disease la (CMT1a): evidence for trisomy of the region p11.2 of chromosome 17 in South Wales families. J Med Genet . 1992;;29:12-13.
43 +
Lupski JR, Pentao L, Williams LL, Patel PI.  Stable inheritance of the CMT1A DNA duplication in two patients with CMT1 and NF1. Am J Med Genet . 1993;;45:92-96.
44 +
Wise CA, Garcia CA, Davis S, et al.  Molecular analyses of unrelated Charcot-Marie-Tooth disease patients suggest a high frequency of the CMT1A duplication. Am J Hum Genet . 1993;;53:853-863.
45 +
Lupski JR, Wise CA, Kuwano A, et al.  Gene dosage is a mechanism for Charcot-Marie-Tooth disease type 1A. Nature Genet . 1992;;1:29-33.
46 +
Chance PF, Bird TD, Matsunami N, Lensch MW, Brothman AR, Feldman GF.  Trisomy 17p associated with Charcot-Marie-Tooth neuropathy type 1A phenotype: evidence for gene dosage as a mechanism in CMT1A. Neurology . 1992;;42:2295-2299.
47 +
Upadhyaya M, Roberts SH, Farnham J, et al.  Charcot-Marie-Tooth disease type 1A (CMT1A) associated with a maternal duplication of chromosome 17p11.2-12. Hum Genet . 1993;;91:392-395.
48 +
Roa BB, Garcia CA, Wise CA, et al.  Gene dosage as a mechanism for a common autosomal dominant peripheral neuropathy: Charcot-Marie-Tooth disease type 1A.  In: Epstein CJ, ed. Phenotypic Mapping of Down Syndrome and Other Aneuploid Conditions . New York, NY: Wiley-Liss Inc; 1993;:187-205.
49 +
Lupski JR.  An inherited DNA rearrangement and gene dosage effect are responsible for the most common autosomal dominant peripheral neuropathy: Charcot-Marie-Tooth disease type 1A. Clin Res . 1992;; 40:645-652.
50 +
Killian JM, Kloepfer HW.  Homozygous expression of a dominant gene for Charcot-Marie-Tooth neuropathy. Ann Neurol . 1979;;5:515-522.
51 +
Dejerine J, Sottas J.  Sur la nevrite interstitielle, hypertrophique et progressive de l'enface. C R Seances Soc Biol Fil . 1893;;45:63-96.
52 +
Suter U, Welcher AA, Ozcelik T, et al.  The Trembler mouse carries a point mutation in a myelin gene. Nature . 1992;;356:241-244.
53 +
Suter U, Moskow JJ, Welcher AA, et al.  A leucine to proline mutation in the putative first transmembrane domain of the 22-kDa peripheral myelin protein in the Trembler-J mouse. Proc Natl Acad Sci U S A . 1992;;89:4382-4386.
54 +
Patel PI, Roa BB, Welcher AA, et al.  The gene for the peripheral myelin protein PMP-22 is a candidate for Charcot-Marie-Tooth disease type 1A. Nature Genet . 1992;;1:159-165.
55 +
Matsunami N, Smith B, Ballard L, et al.  Peripheral myelin protein-22 gene maps in the duplication in chromosome 17p11.2 associated with Charcot-Marie-Tooth 1A. Nature Genet . 1992;;1:176-179.
56 +
Valentijn LJ, Bolhuis PA, Zorn I, et al.  The peripheral myelin gene PMP-22/GAS-3 is duplicated in Charcot-Marie-Tooth disease type 1A. Nature Genet . 1992;;1:166-170.
57 +
Timmerman V, Nelis E, Van Hul W, et al.  The peripheral myelin protein gene PMP-22 is contained within the Charcot-Marie-Tooth disease type 1A duplication. Nature Genet . 1992;;1:171-175.
58 +
Hayasaka K, Himoro M, Nanao K, et al.  Isolation and sequence determination of cDNA encoding PMP22 (PAS-IISR13/GAS-3) of human peripheral myelin. Biochem Biophys Res Commun . 1992;;186:827-831.
59 +
Roa BB, Garcia CA, Suter U, et al.  Charcot-Marie-Tooth disease type 1A: association with a spontaneous point mutation in the PMP22 gene. N Engl J Med . 1993;;329:96-101.
60 +
Valentijn LJ, Baas F, Wolterman RA, et al.  Identical point mutations of PMP-22 in TremblerJ mouse and Charcot-Marie-Tooth disease type 1A. Nature Genet . 1992;;2:288-291.
61 +
Roa BB, Dyck PJ, Marks HG, Chance PF, Lupski JR.  Dejerine-Sottas syndrome associated with point mutation in the peripheral myelin protein 22 (PMP22) gene. Nature Genet . 1993;;5:269-273.
62 +
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To understand the clinical management of acute heart failure syndromes.
Accreditation Information The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
To view and print your certificate and access a summary of your CME courses go to My CME.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
Cone
AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
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