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PMID: 8755926 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1.

American journal of human genetics ·Vol. 59 ·No. 2 ·1996-08-00 ·Pages 392-9

Flanigan K, Gardner K, Alderson K, Galster B, Otterud B, Leppert MF, Kaplan C, Ptácek LJ

Abstract

The hereditary ataxias represent a clinically and genetically heterogeneous group of neurodegenerative disorders. Various classification schemes based on clinical criteria are being replaced as molecular characterization of the ataxias proceeds; so far, seven distinct autosomal dominant hereditary ataxias have been genetically mapped in the human genome. We report linkage to chromosome 16q22.1 for one of these genes (SCA4) in a five-generation family with an autosomal dominant, late-onset spinocerebellar ataxia; the gene is tightly linked to the microsatellite marker D16S397 (LOD score = 5.93 at theta = .00). In addition, we present clinical and electrophysiological data regarding the distinct and previously unreported phenotype consisting of ataxia with the invariant presence of a prominent axonal sensory neuropathy.

MeSH Terms
Axons/pathology Chromosomes, Human, Pair 16 Female Genes, Dominant Genetic Markers Haplotypes Hereditary Sensory and Autonomic Neuropathies/classification,ethnology,genetics Humans Lod Score Male Pedigree Scandinavian and Nordic Countries/ethnology Spinocerebellar Degenerations/classification,ethnology,genetics Utah/epidemiology Wyoming/epidemiology
Chemicals
Genetic Markers
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Flanigan K
Department of Neurology, University of Utah Medical Center, Salt Lake City 84112, USA.
Gardner K
Alderson K
Galster B
Otterud B
Leppert M F
Kaplan C
Ptácek L J
References (33)
33 references, click to expand
  1. Molecular and clinical correlations in spinocerebellar ataxia type 3 and Machado-Joseph disease.
    Ann Neurol. 1995 Jul;38(1):68-72 PMID: 7611728
  2. A single ataxia telangiectasia gene with a product similar to PI-3 kinase.
    Science. 1995 Jun 23;268(5218):1749-53 PMID: 7792600
  3. Retinal degeneration characterizes a spinocerebellar ataxia mapping to chromosome 3p.
    Nat Genet. 1995 May;10(1):89-93 PMID: 7647799
  4. Expression analysis of the ataxin-1 protein in tissues from normal and spinocerebellar ataxia type 1 individuals.
    Nat Genet. 1995 May;10(1):94-8 PMID: 7647801
  5. Adult-onset spinocerebellar dysfunction caused by a mutation in the gene for the alpha-tocopherol-transfer protein.
    N Engl J Med. 1995 Nov 16;333(20):1313-8 PMID: 7566022
  6. Machado-Joseph disease and SCA3: the genotype meets the phenotypes.
    Neurology. 1996 Jan;46(1):4-8 PMID: 8559417
  7. Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion.
    Science. 1996 Mar 8;271(5254):1423-7 PMID: 8596916
  8. [Radiculo-posterior cord form of spinocerebellar degeneration].
    Rev Neurol (Paris). 1954;91(1):3-21 PMID: 14358114
  9. The olivopontocerebellar atrophies: a review.
    Medicine (Baltimore). 1970 May;49(3):227-41 PMID: 4910986
  10. A new form of heredo-familial spinocerebellar degeneration with slow eye movements (nine families).
    Brain. 1971;94(2):359-74 PMID: 5571047
  11. Autosomal dominant system degeneration in Portuguese families of the Azores Islands. A new genetic disorder involving cerebellar, pyramidal, extrapyramidal and spinal cord motor functions.
    Neurology. 1978 Jul;28(7):703-9 PMID: 566869
  12. Peripheral neuropathy in spinocerebellar degenerations.
    Muscle Nerve. 1981 Jan-Feb;4(1):51-61 PMID: 7231446
  13. Multilocus linkage analysis in humans: detection of linkage and estimation of recombination.
    Am J Hum Genet. 1985 May;37(3):482-98 PMID: 3859205
  14. Spinocerebellar ataxia: variable age of onset and linkage to human leukocyte antigen in a large kindred.
    Ann Neurol. 1988 Jun;23(6):580-4 PMID: 3165612
  15. Autosomal dominant ataxia: genetic evidence for locus heterogeneity from a Cuban founder-effect population.
    Am J Hum Genet. 1990 Jun;46(6):1163-77 PMID: 1971152
  16. Autosomal dominant cerebellar ataxia: clinical analysis of 263 patients from a homogeneous population in Holguín, Cuba.
    Neurology. 1990 Sep;40(9):1369-75 PMID: 2392220
  17. The gene for autosomal dominant spinocerebellar ataxia (SCA1) maps telomeric to the HLA complex and is closely linked to the D6S89 locus in three large kindreds.
    Am J Hum Genet. 1991 Jul;49(1):23-30 PMID: 2063871
  18. Localization of the autosomal dominant HLA-linked spinocerebellar ataxia (SCA1) locus, in two kindreds, within an 8-cM subregion of chromosome 6p.
    Am J Hum Genet. 1991 Jul;49(1):31-41 PMID: 1676561
  19. Analysis in a large hyperkalemic periodic paralysis pedigree supports tight linkage to a sodium channel locus.
    Am J Hum Genet. 1991 Aug;49(2):378-82 PMID: 1651050
  20. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1.
    Nat Genet. 1993 Jul;4(3):221-6 PMID: 8358429
  21. Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23-24.1.
    Nat Genet. 1993 Jul;4(3):295-9 PMID: 8358438
  22. Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p.
    Nat Genet. 1994 Jan;6(1):14-8 PMID: 8136826
  23. Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA).
    Nat Genet. 1994 Jan;6(1):9-13 PMID: 8136840
  24. The 1993-94 Généthon human genetic linkage map.
    Nat Genet. 1994 Jun;7(2 Spec No):246-339 PMID: 7545953
  25. The trinucleotide repeat expansion on chromosome 6p (SCA1) in autosomal dominant cerebellar ataxias.
    Brain. 1994 Aug;117 ( Pt 4):645-9 PMID: 7922453
  26. Identification and characterization of the gene causing type 1 spinocerebellar ataxia.
    Nat Genet. 1994 Aug;7(4):513-20 PMID: 7951322
  27. Autosomal dominant cerebellar phenotypes: the genotype has settled the issue.
    Neurology. 1995 Jan;45(1):1-5 PMID: 7824096
  28. Analysis of the SCA1 CAG repeat in a large number of families with dominant ataxia: clinical and molecular correlations.
    Ann Neurol. 1995 Feb;37(2):176-80 PMID: 7847859
  29. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1.
    Nat Genet. 1994 Nov;8(3):221-8 PMID: 7874163
  30. Spinocerebellar ataxia type 5 in a family descended from the grandparents of President Lincoln maps to chromosome 11.
    Nat Genet. 1994 Nov;8(3):280-4 PMID: 7874171
  31. Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein.
    Nat Genet. 1995 Feb;9(2):141-5 PMID: 7719340
  32. Molecular cloning and physical and genetic mapping of a novel human Na+/H+ exchanger (NHE5/SLC9A5) to chromosome 16q22.1.
    Genomics. 1995 Feb 10;25(3):615-22 PMID: 7759094
  33. The gene for autosomal dominant cerebellar ataxia with pigmentary macular dystrophy maps to chromosome 3p12-p21.1.
    Nat Genet. 1995 May;10(1):84-8 PMID: 7647798
Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
Published
1996-08-00
Pages
392-9
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1914712
Subset
IM
Grants
NHGRI NIH HHS · 8 RO1 HG00367 · United States
NICHD NIH HHS · K11 HD00940 · United States
NCRR NIH HHS · M01-RR00064 · United States
External Links
PubMed source PMC Full Text View journal details
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