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November 1993, Vol 50, No. 11 >
Article | November 1993

An Introduction to the Molecular Genetics of Neurological Disease: Title and subTitle BreakRecent Advances

Roger N. Rosenberg, MD
Arch Neurol. 1993;50(11):1123-1128. doi:10.1001/archneur.1993.00540110005001
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References
Comments

This Issue of the Archives is devoted to recent achievements in neurogenetics. The past decade has truly been a remarkable time of advancement in this field, and this issue captures some of the excitement and momentum. Leading authorities have been selected to review the current molecular basis of Alzheimer's disease (AD), Huntington's disease (HD), mitochondrial encephalomyopathies, prion diseases, Charcot-Marie-Tooth syndrome, neurofibromatosis, myotonic dystrophy, Duchenne-Becker muscular dystrophy (DMD), Gaucher disease, skeletal muscle sodium-channel diseases, and potential areas of treatment, including gene therapy. The result, in my view, is a superb exposition of the vitality and progress of investigation in understanding these important inherited neurological diseases at the molecular level. A neurological gene map has been included as well, describing the positional chromosome location for each disease as determined by linkage analysis.1-3I shall briefly comment editorially on the progress made in several of these diseases and leave the major discussion

REFERENCES

1 +
McKusick VA. Mendelian Inheritance in Man . 8th ed. Baltimore, Md: Johns Hopkins University Press; 1988;:xi.
2 +
Brady RO, Rosenberg RN.  Autosomal dominant neurological disorders . Ann Neurol . 1978;;4:548-552.
3 +
Rosenberg RN.  Triumph of linkage analysis . Ann Neurol . 1990;;27:111-113.
4 +
Gusella JF, Wexler NS, Conneally PM, et al.  A polymorphic DNA marker genetically linked to Huntington's disease . Nature . 1983;;306:234-238.
5 +
Martin J, Gusella J.  Huntington's disease . N Engl J Med . 1986;;315:1267-1276.
6 +
Hayden M, Hewitt J, Stoessl A, Clark C, Amman W, Martin W.  The combined use of positron emission tomography and DNA polymorphisms for preclinical detection of Huntington's disease . Neurology . 1987;;37:1441-1447.
7 +
Parker WD, Boyson S, Luder A, Parks J.  Evidence for a defect in NADHubiquinone oxidoreductase (complex 1) in Huntington's disease . Neurology . 1990;;40:1231-1234.
8 +
Gusella JF, MacDonald ME, Ambrose CM, Duyao MP.  Molecular genetics of Huntington's disease . Arch Neurol . 1993;;50:1157-1163.
9 +
St George-Hyslop P, Tanzi R, Polinsky R, et al.  The genetic defect causing familial Alzheimer's disease maps on chromosome 21 . Science . 1987;;235: 885-890.
10 +
Schellenberg GD, Bird TD, Wijsman EM, et al.  Genetic linkage evidence for a familial Alzheimer's disease locus on chromosome 14 . Science . 1992;:258:668-671.
11 +
St George-Hyslop P, Haines J, Rogaev E, Mortilla M.  Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14 . Nature Genet . 1992;;2:330-334.
12 +
Van Broeckhoven C, Backhovens H, Cruts M, et al.  Mapping of a gene predisposing to early-onset Alzheimer's disease to chromosome 14q24.3 . Nature Genet . 1992;;2:335-339.
13 +
Pericak-Vance M, Bedout J, Gaskell P, Roses A.  Linkage studies in familial Alzheimer's disease evidence for chromosome 19 linkage . Am J Hum Genet . 1991;;48:1034-1050.
14 +
Tanzi R, Gusella J, Watkins P, et al.  Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus . Science . 1987;;235: 880-884.
15 +
Selkoe D, Poslisny M, Price D, Cork L.  Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer's disease . Science . 1987;;235:873-877.
16 +
16. Selkoe DJ.  Deciphering Alzheimer's disease: the amyloid precursor protein yields new clues . Science . 1990;;248:1058-1060.
17 +
Baskin F, Rosenberg RN, Greenberg BD.  Increased release of an amyloidogenic C-terminal Alzheimer amyloid precursor protein fragment from stressed PC-12 cells . J Neurosci Res . 1991;;29:127-132.
18 +
Baskin F, Rosenberg RN, Davis RM.  Rapid communication: morphological differentiation and proteoglycan synthesis regulate Alzheimer amyloid precursor protein processing in PC-12 and human astrocyte cultures . J Neurosci Res . 1992;;32:274-279.
19 +
Goate A, Chartier-Harlin AM, Mullan M, et al.  Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease . Nature . 1991;;349:704-706.
20 +
Chartier-Harlin MC, Crawford F, Hamandi K, et al.  Screening for the betaamyloid precursor protein mutation (APP717:Val-lle) in extended pedigrees with early onset Alzheimer's disease . Neurosci Lett . 1991;;129:134-135.
21 +
Murrell J, Farlow M, Ghetti B, Benson MD.  A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease . Science . 1991;;254:97-99.
22 +
Karlinsky H, Vaula G, Haines J, et al.  Molecular and prospective phenotypic characterization of a pedigree with familial Alzheimer's disease and a missense mutation in codon 717 of the beta-amyloid precursor protein gene . Neurology . 1992;;42:1445-1453.
23 +
Mullan M, Crawford F, Axelman K, et al.  A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta amyloid . Nature Genet . 1992;;1:345-347.
24 +
Hardy J.  Framing beta amyloid . Nature Genet . 1992;;1:233-234.
25 +
Shoji M, Golde T, Ghiso J, et al.  Production of the Alzheimer amyloid beta protein by normal proteolytic processing . Science . 1992;;258:126-129.
26 +
Haass C, Schlossmacher M, Hung A, et al.  Amyloid beta peptide is produced by cultured cells during normal metabolism . Nature . 1992;;359:322-327.
27 +
Corder EH, Saunders AM, Strittmatter WJ, et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families . Science . 1993;;261:921-923.
28 +
Collins F, Ponder S, Seizinger B, Epstein C.  The von Recklinghausen neurofibromatosis region on chromosome 17: genetic and physical maps come into focus . Am J Hum Genet . 1989;;44:1-5.
29 +
Gutmann DH, Collins FS.  Neurofibromatosis type I: beyond positional cloning . Arch Neurol . 1993;;50:1185-1193.
30 +
Koenig M, Hoffman E, Bertelson C, Monaco A, Freener C, Kunkel L.  Complete cloning of the Duchenne muscular dystrophy cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals . Cell . 1987;; 50:509-517.
31 +
Hoffman E, Brown R, Kunkel L.  Dystrophin: the protein product of the Duchenne muscular dystrophy locus . Cell . 1987;;51:919-928.
32 +
Hoffman E, Fischbeck K, Brown R, et al.  Characterization of dystrophin in musclebiopsy specimens from patients with Duchenne's or Becker's muscular dystrophy . N Engl J Med . 1988;;318:1363-1368.
33 +
Rowland LP.  Clinical concepts of Duchenne muscular dystrophy . Brain . 1988;; 111:479-485.
34 +
Davis MD, Rosenberg RN, Harding AE.  Molecular genetics and neurologic disease . In: Rosenberg RN, Prusiner SB, DiMauro SD, Barchi RL, Kunkel L, eds. The Molecular and Genetic Basis of Neurological Disease . Boston, Mass: Butterworth-Heinemann; 1993;:3-20.
35 +
Hoffman EP, Wang J.  Duchenne-Becker muscular dystrophy and the nondystrophic myotonias: paradigms for loss of function and change of function of gene products . Arch Neurol . 1993;;50:1227-1237.
36 +
Chad D, Munsat T.  Diseases of muscle . In: Rosenberg RN, ed. Comprehensive Neurology . New York, NY: Raven Press; 1991;:457-459.
37 +
Penrose L.  The problem of anticipation in pedigrees of dystrophia myotonica . Ann Eugen (Lond) . 1948;;14:125-132.
38 +
Harley HG, Brook J, Rundle S, et al.  Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy . Nature . 1992;;355:545-546.
39 +
Verkerk A, Pieretti M, Sutcliffe J, et al.  Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome . Cell . 1991;;65:905-914.
40 +
Pergolizzi R, Erster S, Goonewardena P, Brown W.  Detection of full fragile X mutation . Lancet . 1992;;339:271-272.
41 +
La Spada A, Wilson E, Lubahn D, Harding A, Fischbeck K.  Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy . Nature . 1991;; 352:77-79.
42 +
Buxton J, Shelbourne P, Davies J, et al.  Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy . Nature . 1992;;355:547-548.
43 +
Aslanidis C, Jansen G, Amemiya C, et al.  Cloning of the essential myotonic dystrophy region and mapping of the putative defect . Nature . 1992;;355:548-551.
44 +
Mahadevan M, Tsilfidis C, Sabourin L, et al.  Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene . Science . 1992;; 255:1253-1255.
45 +
Fu Y-H, Pizzuti A, Fenwick R Jr, et al.  An unstable triplet repeat in a gene related to myotonic muscular dystrophy . Science . 1992;;255:1256-1258.
46 +
Brook J, McCurrach M, Harley H, et al.  Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript . Cell . 1992;;68:799-808.
47 +
Rosenberg RN.  Amplification signals anticipation: less DNA is better . Neurology . 1992;;42:1857-1858.
48 +
Pizzuti A, Friedman DL, Caskey CT.  The myotonic dystrophy gene . Arch Neurol . 1993;;50:1173-1179.
49 +
Lupski JR, Wise CA, Kuwano A, Pentao L, et al.  Gene dosage is a mechanism for Charcot-Marie-Tooth disease type 1A . Nature Genet . 1992;;1:29-33.
50 +
Chance PF, Pleasure D.  Charcot-Marie-Tooth syndrome . Arch Neurol . 1993;; 50:1180-1184.
51 +
Jackson J, Currier R, Terasaki P, Morton N.  Spinocerebellar ataxia and HLA linkage: risk predictions by HLA typing . N Engl J Med . 1977;;296:1138-1141.
52 +
Rich S, Wilkie P, Schut L, et al.  Spinocerebellar ataxia: localization of an autosomal dominant locus between two markers on human chromosome 6 . Am J Hum Genet . 1987;;41:524-531.
53 +
Zoghbi H, Pollack M, Lyons L, et al.  Spinocerebellar ataxia . Ann Neurol . 1988;; 23:580-584.
54 +
Zoghbi H, Sandkugl L, Ott J, et al.  Assignment of autosomal dominant spinocerebellar ataxia (SCA1) centromeric to the HLA region on the short arm of chromosome 6, using multilocus linkage analysis . Am J Hum Genet . 1989;;44:255-263.
55 +
Orr H, Rich S.  Localization of the autosomal dominant, HLA-linked spinocerebellar ataxia (SCA1) locus in two kindreds within a subregion of chromosome 6p . Am J Hum Genet . 1989;;45( (suppl) ):A155.
56 +
Orozo-Diaz G, Capote R.  Autosomal dominant ataxia: genetic evidence for locus heterogeneity from a Cuban founded effect population . Am I Hum Genet . 1990;;46:1163-1177.
57 +
Rosenberg RN.  A neurological gene map . Arch Neurol . 1993;;50:1269-1271.
58 +
Young I, Duckett D.  Familial cerebellar ataxia and possible cosegregation with an inversion in chromosome 4 . J Neurol Neurosurg Psychiatry . 1990;;53:441-442.
59 +
Conner KE, Rosenberg RN.  The hereditary ataxias . In: Rosenberg RN, Prusiner SB, DiMauro S, Barchi RL, Kunkel LM, eds. The Molecular and Genetic Basis of Neurological Disease . Boston, Mass: Butterworth-Heinemann; 1993;:697-736.
60 +
Orr HT, Chung MY, Banfi S, et al.  Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1 . Nature Genet . 1993;;4:221-226.
61 +
Gispert S, Twells R, Orozco G, et al.  Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23-24.1 . Nature Genet . 1993;;4:295-299.
62 +
Takiyama Y, Nishizawa M, Tonaka H, et al.  The gene for Machado-Joseph disease maps to human chromosome 14q . Nature Genet . 1993;;4:300-304.
63 +
Prusiner SB, Carlson GA, DeArmond SJ, et al.  Transmissible and genetic prion diseases of humans and animals . In: Rosenberg RN, Prusiner SB, DiMauro S, Barchi RL, Kunkel LM, eds. The Molecular and Genetic Basis of Neurological Disease . Boston, Mass: Butterworth-Heinemann; 1993;:585-609.
64 +
Prusiner BS.  Genetic and infectious prion diseases . Arch Neurol . 1993;;50: 1129-1153.
65 +
DiMauro S, Moraes CT.  Mitochondrial encephalomyopathies . Arch Neurol . 1993;; 50:1197-1208.
66 +
Rüdel R, Ricker K, Lehmann-Horn F.  Genotype-phenotype correlations in human skeletal muscle sodium channel diseases . Arch Neurol . 1993;;50:1241-1251.
67 +
Rosenberg R, Pettegrew J.  Genetic neurological diseases . In: Rosenberg RN, ed. Comprehensive Neurology . New York, NY: Raven Press; 1991;:chap 2.
68 +
Davis MB, Rosenberg RN, Harding AE.  Molecular genetics and neurologic disease: an introduction . In: Rosenberg RN, Prusiner SB, DiMauro S, Barchi RL, Kunkel LM, eds. The Molecular and Genetic Basis of Neurological Disease . Boston, Mass: Butterworth-Heinemann; 1993;:14-17.
69 +
Brady RO, Barton NW, Grabowski GA, et al.  The role of neurogenetics in Gaucher disease . Arch Neurol . 1993;;50:1212-1226.
70 +
Suhr ST, Gage FH.  Gene therapy for neurological disease . Arch Neurol . 1993;; 50:1252-1268.

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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 +
McKusick VA. Mendelian Inheritance in Man . 8th ed. Baltimore, Md: Johns Hopkins University Press; 1988;:xi.
2 +
Brady RO, Rosenberg RN.  Autosomal dominant neurological disorders . Ann Neurol . 1978;;4:548-552.
3 +
Rosenberg RN.  Triumph of linkage analysis . Ann Neurol . 1990;;27:111-113.
4 +
Gusella JF, Wexler NS, Conneally PM, et al.  A polymorphic DNA marker genetically linked to Huntington's disease . Nature . 1983;;306:234-238.
5 +
Martin J, Gusella J.  Huntington's disease . N Engl J Med . 1986;;315:1267-1276.
6 +
Hayden M, Hewitt J, Stoessl A, Clark C, Amman W, Martin W.  The combined use of positron emission tomography and DNA polymorphisms for preclinical detection of Huntington's disease . Neurology . 1987;;37:1441-1447.
7 +
Parker WD, Boyson S, Luder A, Parks J.  Evidence for a defect in NADHubiquinone oxidoreductase (complex 1) in Huntington's disease . Neurology . 1990;;40:1231-1234.
8 +
Gusella JF, MacDonald ME, Ambrose CM, Duyao MP.  Molecular genetics of Huntington's disease . Arch Neurol . 1993;;50:1157-1163.
9 +
St George-Hyslop P, Tanzi R, Polinsky R, et al.  The genetic defect causing familial Alzheimer's disease maps on chromosome 21 . Science . 1987;;235: 885-890.
10 +
Schellenberg GD, Bird TD, Wijsman EM, et al.  Genetic linkage evidence for a familial Alzheimer's disease locus on chromosome 14 . Science . 1992;:258:668-671.
11 +
St George-Hyslop P, Haines J, Rogaev E, Mortilla M.  Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14 . Nature Genet . 1992;;2:330-334.
12 +
Van Broeckhoven C, Backhovens H, Cruts M, et al.  Mapping of a gene predisposing to early-onset Alzheimer's disease to chromosome 14q24.3 . Nature Genet . 1992;;2:335-339.
13 +
Pericak-Vance M, Bedout J, Gaskell P, Roses A.  Linkage studies in familial Alzheimer's disease evidence for chromosome 19 linkage . Am J Hum Genet . 1991;;48:1034-1050.
14 +
Tanzi R, Gusella J, Watkins P, et al.  Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus . Science . 1987;;235: 880-884.
15 +
Selkoe D, Poslisny M, Price D, Cork L.  Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer's disease . Science . 1987;;235:873-877.
16 +
16. Selkoe DJ.  Deciphering Alzheimer's disease: the amyloid precursor protein yields new clues . Science . 1990;;248:1058-1060.
17 +
Baskin F, Rosenberg RN, Greenberg BD.  Increased release of an amyloidogenic C-terminal Alzheimer amyloid precursor protein fragment from stressed PC-12 cells . J Neurosci Res . 1991;;29:127-132.
18 +
Baskin F, Rosenberg RN, Davis RM.  Rapid communication: morphological differentiation and proteoglycan synthesis regulate Alzheimer amyloid precursor protein processing in PC-12 and human astrocyte cultures . J Neurosci Res . 1992;;32:274-279.
19 +
Goate A, Chartier-Harlin AM, Mullan M, et al.  Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease . Nature . 1991;;349:704-706.
20 +
Chartier-Harlin MC, Crawford F, Hamandi K, et al.  Screening for the betaamyloid precursor protein mutation (APP717:Val-lle) in extended pedigrees with early onset Alzheimer's disease . Neurosci Lett . 1991;;129:134-135.
21 +
Murrell J, Farlow M, Ghetti B, Benson MD.  A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease . Science . 1991;;254:97-99.
22 +
Karlinsky H, Vaula G, Haines J, et al.  Molecular and prospective phenotypic characterization of a pedigree with familial Alzheimer's disease and a missense mutation in codon 717 of the beta-amyloid precursor protein gene . Neurology . 1992;;42:1445-1453.
23 +
Mullan M, Crawford F, Axelman K, et al.  A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta amyloid . Nature Genet . 1992;;1:345-347.
24 +
Hardy J.  Framing beta amyloid . Nature Genet . 1992;;1:233-234.
25 +
Shoji M, Golde T, Ghiso J, et al.  Production of the Alzheimer amyloid beta protein by normal proteolytic processing . Science . 1992;;258:126-129.
26 +
Haass C, Schlossmacher M, Hung A, et al.  Amyloid beta peptide is produced by cultured cells during normal metabolism . Nature . 1992;;359:322-327.
27 +
Corder EH, Saunders AM, Strittmatter WJ, et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families . Science . 1993;;261:921-923.
28 +
Collins F, Ponder S, Seizinger B, Epstein C.  The von Recklinghausen neurofibromatosis region on chromosome 17: genetic and physical maps come into focus . Am J Hum Genet . 1989;;44:1-5.
29 +
Gutmann DH, Collins FS.  Neurofibromatosis type I: beyond positional cloning . Arch Neurol . 1993;;50:1185-1193.
30 +
Koenig M, Hoffman E, Bertelson C, Monaco A, Freener C, Kunkel L.  Complete cloning of the Duchenne muscular dystrophy cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals . Cell . 1987;; 50:509-517.
31 +
Hoffman E, Brown R, Kunkel L.  Dystrophin: the protein product of the Duchenne muscular dystrophy locus . Cell . 1987;;51:919-928.
32 +
Hoffman E, Fischbeck K, Brown R, et al.  Characterization of dystrophin in musclebiopsy specimens from patients with Duchenne's or Becker's muscular dystrophy . N Engl J Med . 1988;;318:1363-1368.
33 +
Rowland LP.  Clinical concepts of Duchenne muscular dystrophy . Brain . 1988;; 111:479-485.
34 +
Davis MD, Rosenberg RN, Harding AE.  Molecular genetics and neurologic disease . In: Rosenberg RN, Prusiner SB, DiMauro SD, Barchi RL, Kunkel L, eds. The Molecular and Genetic Basis of Neurological Disease . Boston, Mass: Butterworth-Heinemann; 1993;:3-20.
35 +
Hoffman EP, Wang J.  Duchenne-Becker muscular dystrophy and the nondystrophic myotonias: paradigms for loss of function and change of function of gene products . Arch Neurol . 1993;;50:1227-1237.
36 +
Chad D, Munsat T.  Diseases of muscle . In: Rosenberg RN, ed. Comprehensive Neurology . New York, NY: Raven Press; 1991;:457-459.
37 +
Penrose L.  The problem of anticipation in pedigrees of dystrophia myotonica . Ann Eugen (Lond) . 1948;;14:125-132.
38 +
Harley HG, Brook J, Rundle S, et al.  Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy . Nature . 1992;;355:545-546.
39 +
Verkerk A, Pieretti M, Sutcliffe J, et al.  Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome . Cell . 1991;;65:905-914.
40 +
Pergolizzi R, Erster S, Goonewardena P, Brown W.  Detection of full fragile X mutation . Lancet . 1992;;339:271-272.
41 +
La Spada A, Wilson E, Lubahn D, Harding A, Fischbeck K.  Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy . Nature . 1991;; 352:77-79.
42 +
Buxton J, Shelbourne P, Davies J, et al.  Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy . Nature . 1992;;355:547-548.
43 +
Aslanidis C, Jansen G, Amemiya C, et al.  Cloning of the essential myotonic dystrophy region and mapping of the putative defect . Nature . 1992;;355:548-551.
44 +
Mahadevan M, Tsilfidis C, Sabourin L, et al.  Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene . Science . 1992;; 255:1253-1255.
45 +
Fu Y-H, Pizzuti A, Fenwick R Jr, et al.  An unstable triplet repeat in a gene related to myotonic muscular dystrophy . Science . 1992;;255:1256-1258.
46 +
Brook J, McCurrach M, Harley H, et al.  Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript . Cell . 1992;;68:799-808.
47 +
Rosenberg RN.  Amplification signals anticipation: less DNA is better . Neurology . 1992;;42:1857-1858.
48 +
Pizzuti A, Friedman DL, Caskey CT.  The myotonic dystrophy gene . Arch Neurol . 1993;;50:1173-1179.
49 +
Lupski JR, Wise CA, Kuwano A, Pentao L, et al.  Gene dosage is a mechanism for Charcot-Marie-Tooth disease type 1A . Nature Genet . 1992;;1:29-33.
50 +
Chance PF, Pleasure D.  Charcot-Marie-Tooth syndrome . Arch Neurol . 1993;; 50:1180-1184.
51 +
Jackson J, Currier R, Terasaki P, Morton N.  Spinocerebellar ataxia and HLA linkage: risk predictions by HLA typing . N Engl J Med . 1977;;296:1138-1141.
52 +
Rich S, Wilkie P, Schut L, et al.  Spinocerebellar ataxia: localization of an autosomal dominant locus between two markers on human chromosome 6 . Am J Hum Genet . 1987;;41:524-531.
53 +
Zoghbi H, Pollack M, Lyons L, et al.  Spinocerebellar ataxia . Ann Neurol . 1988;; 23:580-584.
54 +
Zoghbi H, Sandkugl L, Ott J, et al.  Assignment of autosomal dominant spinocerebellar ataxia (SCA1) centromeric to the HLA region on the short arm of chromosome 6, using multilocus linkage analysis . Am J Hum Genet . 1989;;44:255-263.
55 +
Orr H, Rich S.  Localization of the autosomal dominant, HLA-linked spinocerebellar ataxia (SCA1) locus in two kindreds within a subregion of chromosome 6p . Am J Hum Genet . 1989;;45( (suppl) ):A155.
56 +
Orozo-Diaz G, Capote R.  Autosomal dominant ataxia: genetic evidence for locus heterogeneity from a Cuban founded effect population . Am I Hum Genet . 1990;;46:1163-1177.
57 +
Rosenberg RN.  A neurological gene map . Arch Neurol . 1993;;50:1269-1271.
58 +
Young I, Duckett D.  Familial cerebellar ataxia and possible cosegregation with an inversion in chromosome 4 . J Neurol Neurosurg Psychiatry . 1990;;53:441-442.
59 +
Conner KE, Rosenberg RN.  The hereditary ataxias . In: Rosenberg RN, Prusiner SB, DiMauro S, Barchi RL, Kunkel LM, eds. The Molecular and Genetic Basis of Neurological Disease . Boston, Mass: Butterworth-Heinemann; 1993;:697-736.
60 +
Orr HT, Chung MY, Banfi S, et al.  Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1 . Nature Genet . 1993;;4:221-226.
61 +
Gispert S, Twells R, Orozco G, et al.  Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23-24.1 . Nature Genet . 1993;;4:295-299.
62 +
Takiyama Y, Nishizawa M, Tonaka H, et al.  The gene for Machado-Joseph disease maps to human chromosome 14q . Nature Genet . 1993;;4:300-304.
63 +
Prusiner SB, Carlson GA, DeArmond SJ, et al.  Transmissible and genetic prion diseases of humans and animals . In: Rosenberg RN, Prusiner SB, DiMauro S, Barchi RL, Kunkel LM, eds. The Molecular and Genetic Basis of Neurological Disease . Boston, Mass: Butterworth-Heinemann; 1993;:585-609.
64 +
Prusiner BS.  Genetic and infectious prion diseases . Arch Neurol . 1993;;50: 1129-1153.
65 +
DiMauro S, Moraes CT.  Mitochondrial encephalomyopathies . Arch Neurol . 1993;; 50:1197-1208.
66 +
Rüdel R, Ricker K, Lehmann-Horn F.  Genotype-phenotype correlations in human skeletal muscle sodium channel diseases . Arch Neurol . 1993;;50:1241-1251.
67 +
Rosenberg R, Pettegrew J.  Genetic neurological diseases . In: Rosenberg RN, ed. Comprehensive Neurology . New York, NY: Raven Press; 1991;:chap 2.
68 +
Davis MB, Rosenberg RN, Harding AE.  Molecular genetics and neurologic disease: an introduction . In: Rosenberg RN, Prusiner SB, DiMauro S, Barchi RL, Kunkel LM, eds. The Molecular and Genetic Basis of Neurological Disease . Boston, Mass: Butterworth-Heinemann; 1993;:14-17.
69 +
Brady RO, Barton NW, Grabowski GA, et al.  The role of neurogenetics in Gaucher disease . Arch Neurol . 1993;;50:1212-1226.
70 +
Suhr ST, Gage FH.  Gene therapy for neurological disease . Arch Neurol . 1993;; 50:1252-1268.

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To understand the clinical management of acute heart failure syndromes.
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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.
Note: You must get at least of the answers correct to pass this quiz.
Note: You must get at least of the answers correct to pass this quiz.
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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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