Late onset autosomal dominant cerebellar ataxia a family description and linkage analysis with the hla system

Arruda, Walter O.; Petzl-Erler, M. Luiza; Cardoso, Moema A.; Lehner, Thomas; Ott, Jurg

doi:10.1590/S0004-282X1991000300009

Abstracts

A family suffering an autosomal dominant form of late onset hereditary cerebellar ataxia is described. Eight affected family members were personally studied, and data from another four were obtained through anamnesis. The mean age of onset was 37.1±5.4 years (27-47 years). The clinical picture consisted basically of a pure ataxic cerebellar syndrome. CT-scan disclosed diffuse cerebellar atrophy with relative sparing of the brainstem (and no involvement of supratentorial structures. Neurophysiological studies (nerve conduction, VEP and BAEP) were normal. Twenty-six individuals were typed for HLA histocompatibility antigens. Lod scores were calculated with the computer program LINKMAP. Close linkage of the ataxia gene with the HLA system in this family could be excluded - 0==0,02, z=(-2,17) - and the overall analysis of the lod scores suggest another chromossomal location than chromosome 6.

Descreve-se uma família afetada por forma autossômica dominante de ataria cerebelar de início tardio (acima dos 20 anos). Oito membros da família são estudados e dados de outros quatro afetados pela doença foram obtidos por anamnese. A média de idade de início da doença foi 37,1±5,4 anos (27-47 anos). O quadro clínico consistia basicamente de síndrome cerebelar de caráter lentamente progressivo, sem ocorrência concomitante de sinais ou sintomas decorrentes de envolvimento de outros sistemas. Estudo tomográfico computadorizado mostrava atrofia cerebelar difusa com relativa preservação do tronco cerebral e das estruturas supratentoriais. Estudos neurofisiolôgicos (neurocondução motora/sensitiva, potenciais evocados visuais e auditivos) foram normais. Vinte e seis pessoas da família foram tipados para antígenos de histocompatibilidade HLA. Escores lod foram calculados utilizando programa de computador denominado LINKMAP. Ligação estreita com o sistema HLA nesta família foi excluída - 0==0,02, z=(-2,17) - e a análise global dos escores lod sugerem que o gene mutante nesta família não se localiza no cromossomo 6.

CONTENTS CONTEÚDO

Walter O. ArrudaI; M. Luiza Petzl-ErlerII; Moema A. CardosoI; Thomas LehnerIII; Jurg OttIII

IFrom the Department of Neurology, Unidade de Ciências Neurológicas - New York, USA

IIDepartment of Genetics, Universidade Federal do Paraná

IIICuritiba, Brazil, and Institute of Psychiatry, Columbia University

SUMMARY

A family suffering an autosomal dominant form of late onset hereditary cerebellar ataxia is described. Eight affected family members were personally studied, and data from another four were obtained through anamnesis. The mean age of onset was 37.1±5.4 years (27-47 years). The clinical picture consisted basically of a pure ataxic cerebellar syndrome. CT-scan disclosed diffuse cerebellar atrophy with relative sparing of the brainstem (and no involvement of supratentorial structures. Neurophysiological studies (nerve conduction, VEP and BAEP) were normal. Twenty-six individuals were typed for HLA histocompatibility antigens. Lod scores were calculated with the computer program LINKMAP. Close linkage of the ataxia gene with the HLA system in this family could be excluded - 0==0,02, z=(-2,17) - and the overall analysis of the lod scores suggest another chromossomal location than chromosome 6.

RESUMO

Descreve-se uma família afetada por forma autossômica dominante de ataria cerebelar de início tardio (acima dos 20 anos). Oito membros da família são estudados e dados de outros quatro afetados pela doença foram obtidos por anamnese. A média de idade de início da doença foi 37,1±5,4 anos (27-47 anos). O quadro clínico consistia basicamente de síndrome cerebelar de caráter lentamente progressivo, sem ocorrência concomitante de sinais ou sintomas decorrentes de envolvimento de outros sistemas. Estudo tomográfico computadorizado mostrava atrofia cerebelar difusa com relativa preservação do tronco cerebral e das estruturas supratentoriais. Estudos neurofisiolôgicos (neurocondução motora/sensitiva, potenciais evocados visuais e auditivos) foram normais. Vinte e seis pessoas da família foram tipados para antígenos de histocompatibilidade HLA. Escores lod foram calculados utilizando programa de computador denominado LINKMAP. Ligação estreita com o sistema HLA nesta família foi excluída - 0==0,02, z=(-2,17) - e a análise global dos escores lod sugerem que o gene mutante nesta família não se localiza no cromossomo 6.

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Acknowledgments - We thank Prof. Luiz A. Franco de Andrade, Escola Paulista de Medicina, and Prof. Luiz A. Bascheschi, Universidade de São Paulo, São Paulo, for their helpful suggestions. Dr. Ricardo R. Seixias performed the electrophysiological studies.

Dr. Walter O. Arruda - Unidade de Ciências Neurológicas - Rua Gonçalves Dias 713 - 80240 Curitiba PR - Brasil.

1. Arruda WO. Ataxia Cerebelar Hereditária Autossômica Dominante. Dissertação de Mestrado. Universidade Federal do Paraná, Curitiba, 1989.
2. Arruda WO, Petz-Erler ML, Cardoso, MA, Seixas RR, Lehner T, Ott J. Late-onset autosomal dominant cerebellar ataxia: description of a family with HLA typing (abstract). Neurology 1990, 40(Supl 1):439.
3. Bale AE, Bale SJ, Schlesinger SL, McFarland HF. Linkage analysis in spinopontine atrophy: correlation of HLA linkage with phenotypic findings in hereditary ataxia. Am J Med Genetics 1987, 27:595.
4. Barbeau A, Sadibelouiz M, Sadibelouiz A, Roy M. A clinical classification of hereditary ataxias. Can J Neurol Sci 1984, 11:501.
5. Bodmer WF, Bodmer J. Cytofluorochromasia. In Ray JG Jr, Hare DB, Pedersen PD, Mullaly DI (eds) : NIAID Manual of Tissue Typing Techniques. Drew Publications Nr (NIH) 1978, 78-545.
6. Boyum A. Separation of leukocytes from blood and bone marrow. Scand J. Lab Invest 1968, 21:1.
7. Currier RD, Glover G, Jackson JF, Tipton AF. Spinocerebellar ataxia: study of a large kindred. I. General information and genetics. Neurology 1972, 22:1040.
8. Dawson DM, Feudo P, Zubick HH, Rosenberg R, Fowler H. Electro-oculographic findings in Machado-Joseph disease. Neurology 1982, 32:1272.
9. Greenfield JG. The Spino-Cerebellar Degenerations. Oxford: Blacweli, 1954.
10. Haines JN, Schut LJ, Weitkamp LR, Trayer M, Anderson VE. Spinocerebellar ataxia in a large kindred: age at onset, reproduction, and genetic linkage studies. Neurology 1984, 34:1542.
11. Hall B, Noad KB, Latham O. Familial cortical cerebellar atrophy. Brain 1941, 64:178.
12. Harding AE. The clinical features and classification of the late onset autosomal dominant cerebellar ataxias: a study of 11 families, including descendants of the ş«Drew family of Walworth». Brain 1982, 105:1.
13. Harding AE. Classification of the hereditary ataxias and paraplegias. Lancet 1983, 1:1151.
14. Harding AE. The Hereditary Ataxias and Related Disorders. London: Churchill--Livingstone, 1984.
15. Hoffmann PM, Stuart WH, Earle KM, Brody JA. Hereditary late-onset cerebellar degeneration. Neurology 1971, 21 : 771.
16. Hotson JR, Langston EB, Louis AA, Rosenberg RN. The search for a psysiologic marker of Machado-Joseph disease. Neurology 1987, 37 : 112.
17. Jackson JF, Currier RD, Terasaki PI, Morton NE. Spinocerebellar ataxia and HLA linkage: risk prediction by HLA typing. N Engl J Med 1977, 296-1138.
18. Koeppen AH, Goedde W, Hiller C, Hirth L, Benkmann HS. Hereditary ataxia and the sixth chromossome. Arch Neurol 1981, 38:158.
19. Konigsmark BW, Weiner LP. The olivopontocerebellar atrophies: a review. Medicine 1970, 49:227.
20. Kumar D, Blank CE, Gelsthorpe K. Hereditary cerebellar ataxia and genetic linkage with HLA. Hum Genet 1986, 72:327.
21. Lothrop GM, Lolociel JM, Julien C, Ott J. Strategies for multilocus linkage analysis in humans. Proc Nat Acad Sci USA 1984, 81 : 3443.
22. Marie P. Sur l'hérédoataxie cérébelleuse. Sem Med (Paris) 1893, 13:444.
23. Moeller E, Hindfeld B, Olsson JE. HLA-determination in families with hereditary ataxia. Tissue Antigens 1978, 12 : 337.
24. Morton NE, Lalouel JM, Jackson JF, Currier RD, Yee S. Linkage studies in spinocerebellar ataxia (SCA). Am J Med Genetics 1980, 6:251.
25. Nino H, Noreen HJ, Dubey DP. A family with hereditary ataxia: HLA typing. Neurology 1980, 30:12.
26. Oppenheimer DR. Diseases of the basal ganglia, cerebellum and motor neurons. In Adams JH, Corsellis JAN, Duchen LW: Greenfield's Neuropathology. London: Edward Arnold, 1984.
27. Pedersen L, Platz P. Ryder LP, Lamm LU, Dissing J. A linkage study of hereditary ataxias and related disorders. Evidence of heterogeneity of dominant cerebellar ataxia, Hum Genet 1980, 54:371.
28. Pourcher E, Barbeau A. Field testing of an ataxia scoring and staging system. Can J Neurol Sci 1980, 7:339.
29. Rich SS, Wilkie P, Schut L, Vance G, Orr HT. Spinocerebellar ataxia: localization of an autosomal dominant locus between two markers on human chromosome 6. Am J Hum Genet 1987, 41:524.
30. Richter RB. Late cortical cerebellar atrophy: a form of hereditary cerebellar ataxia. Am J Hum Genetics 1950, 2:1.
31. Rosenberg RN, Grossman A. Hereditary ataxia. Neurol Clin 1989, 7:25.
32. Stone TT. Primary familial degeneration of the cerebellum: report of two cases. J Nerv Mental Dis 1933, 78:131.
33. Van Rossum J, Veenema H, Went LN. Linkage investigations in two families with hereditary ataxia. J Neurol Neurosurg Psychiat 1981, 44:516.
34. Wastiaux JP, Lamourex G, Bouchard JP, Durivage A, Barbeau C, Barbeau A. HLA and complement typing in olivopontocerebellar atrophy. Can J Neurol Sci 1978, 5:75.
35. Weber FP, Greenfield JG. Cerebello-olivary degeneration: an example of heredo-familial incidence. Brain 1942, 65:220.
36. Whittington JE, Keats BJB, Jackson JF, Currier RD, Terasaki PI. Linkage studies on glyoxaliase-1 (GLO), pepsinogen (PG), spinocerebellar ataxia (SCA I), and HLA. Cy-togenet Cell Genet 1980, 28:145.
37. Yakura H. Wakisaka A, Fukimoto S, Itakura I. Hereditary ataxia and HL-A genotypes. N Engl J Med 1974, 291:154.
38. Zee DS, Yee RD, Cogan DG, Robinson DA, Engel WK. Ocular motor abnormalities in hereditary cerebellar ataxia. Brain 1976, 99:207.
39. Zoghbi HY, Pollack MS, Lyons RA, Ferrell RE, Daiger SP, Beaudet AL. Spinocerebellar ataxia: variable age of onset and linkage to HLA in a large kindred. Ann Neurol 1988, 23:580.
40. Zoghbi HY, Sandkuyl LA, Ott J, Daiger SP, Pollack M, O'Brien WE, Beaudet AL. Assignment of autosomal dominant spinocerebellar ataxia (SCA-1) centromeric to the HLA region on the short arm of chromossome 6, using multilocus linkage analysis. Am J Hum Genet 1989, 44:255.

Late onset autosomal dominant cerebellar ataxia a family description and linkage analysis with the hla system

Ataxia cerebelar hereditária de início tardio: descrição de uma família com estudo de ligação com o sistema HLA.

Publication Dates

Publication in this collection
22 Feb 2011
Date of issue
Sept 1991

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Arruda WO. Ataxia Cerebelar Hereditária Autossômica Dominante. Dissertação de Mestrado. Universidade Federal do Paraná, Curitiba, 1989.

[2] 2. Arruda WO, Petz-Erler ML, Cardoso, MA, Seixas RR, Lehner T, Ott J. Late-onset autosomal dominant cerebellar ataxia: description of a family with HLA typing (abstract). Neurology 1990, 40(Supl 1):439.

[3] 3. Bale AE, Bale SJ, Schlesinger SL, McFarland HF. Linkage analysis in spinopontine atrophy: correlation of HLA linkage with phenotypic findings in hereditary ataxia. Am J Med Genetics 1987, 27:595.

[4] 4. Barbeau A, Sadibelouiz M, Sadibelouiz A, Roy M. A clinical classification of hereditary ataxias. Can J Neurol Sci 1984, 11:501.

[5] 5. Bodmer WF, Bodmer J. Cytofluorochromasia. In Ray JG Jr, Hare DB, Pedersen PD, Mullaly DI (eds) : NIAID Manual of Tissue Typing Techniques. Drew Publications Nr (NIH) 1978, 78-545.

[6] 6. Boyum A. Separation of leukocytes from blood and bone marrow. Scand J. Lab Invest 1968, 21:1.

[7] 7. Currier RD, Glover G, Jackson JF, Tipton AF. Spinocerebellar ataxia: study of a large kindred. I. General information and genetics. Neurology 1972, 22:1040.

[8] 8. Dawson DM, Feudo P, Zubick HH, Rosenberg R, Fowler H. Electro-oculographic findings in Machado-Joseph disease. Neurology 1982, 32:1272.

[9] 9. Greenfield JG. The Spino-Cerebellar Degenerations. Oxford: Blacweli, 1954.

[10] 10. Haines JN, Schut LJ, Weitkamp LR, Trayer M, Anderson VE. Spinocerebellar ataxia in a large kindred: age at onset, reproduction, and genetic linkage studies. Neurology 1984, 34:1542.

[11] 11. Hall B, Noad KB, Latham O. Familial cortical cerebellar atrophy. Brain 1941, 64:178.

[12] 12. Harding AE. The clinical features and classification of the late onset autosomal dominant cerebellar ataxias: a study of 11 families, including descendants of the ş«Drew family of Walworth». Brain 1982, 105:1.

[13] 13. Harding AE. Classification of the hereditary ataxias and paraplegias. Lancet 1983, 1:1151.

[14] 14. Harding AE. The Hereditary Ataxias and Related Disorders. London: Churchill--Livingstone, 1984.

[15] 15. Hoffmann PM, Stuart WH, Earle KM, Brody JA. Hereditary late-onset cerebellar degeneration. Neurology 1971, 21 : 771.

[16] 16. Hotson JR, Langston EB, Louis AA, Rosenberg RN. The search for a psysiologic marker of Machado-Joseph disease. Neurology 1987, 37 : 112.

[17] 17. Jackson JF, Currier RD, Terasaki PI, Morton NE. Spinocerebellar ataxia and HLA linkage: risk prediction by HLA typing. N Engl J Med 1977, 296-1138.

[18] 18. Koeppen AH, Goedde W, Hiller C, Hirth L, Benkmann HS. Hereditary ataxia and the sixth chromossome. Arch Neurol 1981, 38:158.

[19] 19. Konigsmark BW, Weiner LP. The olivopontocerebellar atrophies: a review. Medicine 1970, 49:227.

[20] 20. Kumar D, Blank CE, Gelsthorpe K. Hereditary cerebellar ataxia and genetic linkage with HLA. Hum Genet 1986, 72:327.

[21] 21. Lothrop GM, Lolociel JM, Julien C, Ott J. Strategies for multilocus linkage analysis in humans. Proc Nat Acad Sci USA 1984, 81 : 3443.

[22] 22. Marie P. Sur l'hérédoataxie cérébelleuse. Sem Med (Paris) 1893, 13:444.

[23] 23. Moeller E, Hindfeld B, Olsson JE. HLA-determination in families with hereditary ataxia. Tissue Antigens 1978, 12 : 337.

[24] 24. Morton NE, Lalouel JM, Jackson JF, Currier RD, Yee S. Linkage studies in spinocerebellar ataxia (SCA). Am J Med Genetics 1980, 6:251.

[25] 25. Nino H, Noreen HJ, Dubey DP. A family with hereditary ataxia: HLA typing. Neurology 1980, 30:12.

[26] 26. Oppenheimer DR. Diseases of the basal ganglia, cerebellum and motor neurons. In Adams JH, Corsellis JAN, Duchen LW: Greenfield's Neuropathology. London: Edward Arnold, 1984.

[27] 27. Pedersen L, Platz P. Ryder LP, Lamm LU, Dissing J. A linkage study of hereditary ataxias and related disorders. Evidence of heterogeneity of dominant cerebellar ataxia, Hum Genet 1980, 54:371.

[28] 28. Pourcher E, Barbeau A. Field testing of an ataxia scoring and staging system. Can J Neurol Sci 1980, 7:339.

[29] 29. Rich SS, Wilkie P, Schut L, Vance G, Orr HT. Spinocerebellar ataxia: localization of an autosomal dominant locus between two markers on human chromosome 6. Am J Hum Genet 1987, 41:524.

[30] 30. Richter RB. Late cortical cerebellar atrophy: a form of hereditary cerebellar ataxia. Am J Hum Genetics 1950, 2:1.

[31] 31. Rosenberg RN, Grossman A. Hereditary ataxia. Neurol Clin 1989, 7:25.

[32] 32. Stone TT. Primary familial degeneration of the cerebellum: report of two cases. J Nerv Mental Dis 1933, 78:131.

[33] 33. Van Rossum J, Veenema H, Went LN. Linkage investigations in two families with hereditary ataxia. J Neurol Neurosurg Psychiat 1981, 44:516.

[34] 34. Wastiaux JP, Lamourex G, Bouchard JP, Durivage A, Barbeau C, Barbeau A. HLA and complement typing in olivopontocerebellar atrophy. Can J Neurol Sci 1978, 5:75.

[35] 35. Weber FP, Greenfield JG. Cerebello-olivary degeneration: an example of heredo-familial incidence. Brain 1942, 65:220.

[36] 36. Whittington JE, Keats BJB, Jackson JF, Currier RD, Terasaki PI. Linkage studies on glyoxaliase-1 (GLO), pepsinogen (PG), spinocerebellar ataxia (SCA I), and HLA. Cy-togenet Cell Genet 1980, 28:145.

[37] 37. Yakura H. Wakisaka A, Fukimoto S, Itakura I. Hereditary ataxia and HL-A genotypes. N Engl J Med 1974, 291:154.

[38] 38. Zee DS, Yee RD, Cogan DG, Robinson DA, Engel WK. Ocular motor abnormalities in hereditary cerebellar ataxia. Brain 1976, 99:207.

[39] 39. Zoghbi HY, Pollack MS, Lyons RA, Ferrell RE, Daiger SP, Beaudet AL. Spinocerebellar ataxia: variable age of onset and linkage to HLA in a large kindred. Ann Neurol 1988, 23:580.

[40] 40. Zoghbi HY, Sandkuyl LA, Ott J, Daiger SP, Pollack M, O'Brien WE, Beaudet AL. Assignment of autosomal dominant spinocerebellar ataxia (SCA-1) centromeric to the HLA region on the short arm of chromossome 6, using multilocus linkage analysis. Am J Hum Genet 1989, 44:255.