TRINUCLEOTIDE EXPANSION WITHIN THE MJD1 GENE PRESENTS CLINICALLY AS SPINOCEREBELLAR ATAXIA AND OCCURS MOST FREQUENTLY IN GERMAN SCA PATIENTS

被引：109

作者：

SCHOLS, L

VIEIRASAECKER, AMM

SCHOLS, S

PRZUNTEK, H

EPPLEN, JT

RIESS, O

机构：

[1] ST JOSEF HOSP,DEPT NEUROL,BOCHUM,GERMANY

[2] RUHR UNIV BOCHUM,D-44780 BOCHUM,GERMANY

来源：

HUMAN MOLECULAR GENETICS | 1995年 / 4卷 / 06期

关键词：

D O I：

10.1093/hmg/4.6.1001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Autosomal dominant spinocerebellar ataxia (SCA) is a clinically and genetically heterogeneous neurodegenerative disorder which leads to progressive cerebellar ataxia, A gene responsible for SCA type 3 has been mapped to human chromosome 14q, close to the Machado-Joseph disease (MJD) locus. The MJD1 gene has recently been cloned and the disease causing mutation has been identified as an unstable and expanded (GAG)(n) trinucleotide repeat. As some clinical features of MJD overlap with those of SCA we investigated the MJD mutation in 38 German families with dominantly inherited SCA. The MJD1 (GAG)(n) expansion was identified in 19 families, In contrast, the trinucleotide expansion was not observed in 21 ataxia patients without family history of the disease, Analysis of the (GAG)(n) repeat length in 30 patients revealed an inverse correlation with the age of onset, The (GAG)(n) stretch of the affected allele varied between 67 and 78 trinucleotide units, the normal alleles carried between 12 and 28 simple repeats, These results demonstrate that the MJD mutation causes the disease phenotype of most SCA patients in Germany.

引用

页码：1001 / 1005

页数：5

共 32 条

[1]

Orr H.T., Chung M.-Y., Banfi S., Kwiatkowski T.J., Servadio A., Beaudet A.L., McCall A.E., Duvick L.A., Ranum L.P.W., Zoghbi H.Y., Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1, Nature Genet., 4, pp. 221-226, (1993)

[2]

Banfi S., Chung M.-Y., Kwiatkowski T.J., Ranum L.P.W., McCall A.E., Chinault A.C., Orr H.T., Zoghbi H.Y., Mapping and cloning of the critical region for the spinocerebellar ataxia type 1 gene in a yeast artificial chromosome contig spanning 1.2 Mb, Genomics, 18, pp. 627-635, (1993)

[3]

Silveira I., Manaia A., Melki J., Magarino C., Lunkes A., Hernandez A., Gispert S., Burlet P., Rozet J.-M., Coutinho P., Leal Loureiro J.E., Guimaraes J., Auburger G., Munnich A., Sequiros J., Machado-Joseph disease is genetically different from Holguin dominant ataxia (SCA2), Genomics, 17, pp. 556-559, (1993)

[4]

Gardner K., Alderson K., Galster B., Kaplan C., Leppert M., Ptacek L., Autosomal dominant spinocerebellar ataxia: Clinical description of a distinct hereditary ataxia and genetic localization to chromosome 16 (SCA4) in a Utah kindred, Neurology, 44, (1994)

[5]

Ranum L.P.W., Schul L.J., Lundgren J.K., Orr H.T., Livingston D.M., Spinocerebellar ataxia type 5 in a family descended from the grandparents of President Lincoln maps to chromosome 11, Nature Genet., 8, pp. 280-284, (1994)

[6]

Stevanin G., Le Guern E., Ravise N., Chneiweiss H., Durr A., Cancel G., Vignal A., Boch A.-L., Ruberg M., Penet C., Pothin Y., Lagroua L., Haguenau M., Rancurel G., Weissenbach J., Agid Y., Brice A., A third locus for autosomal dominant cerebellar ataxia type I maps to chromosome I4q24.3-qter: Evidence for the existence of a fourth locus, Am. J. Hum. Genet., 54, pp. 11-20, (1994)

[7]

St George-Hyslop P., Rogaeva E., Huterer J., Tsuda T., Santos J., Haines J.L., Schlumpf K., Rogaev E.L., Liang Y., Crapper McLachlan D.R., Kennedy J., Weissenbach J., Billingsley G.D., Cox D.W., Lang A.E., Wherret J.R., Machado-Joseph disease in pedigrees of Azorean descent is linked to chromosome 14, Am. J. Hum. Genet., 55, pp. 120-125, (1994)

[8]

Takiyama Y., Nishizawa M., Tanaka H., Kawashima S., Sakamoto H., Karube Y., Shimazaki H., Soutome M., Endo K., Ohta S., Kagawa Y., Kanazawa I., Mizuno Y., Yoshida M., Yuasa T., Horikawa Y., Oyanagi K., Nagai H., Kondo T., Inuzuka T., Onodera O., Tsuji S., The gene for Machado-Joseph disease maps to human chromosome 14q, Nature Genet., 4, pp. 300-304, (1993)

[9]

Nakano K.K., Dawson D.M., Spence A., Machado disease: A hereditary ataxia in Portuguese immigrants to Massachusetts, Neurology, 22, pp. 49-55, (1972)

[10]

Woods B.I., Schaumburg H.H., Nigro-spino-dentatal degeneration with nuclear ophthalmoplegia: A unique and partially treatable clinicopathological entity, J. Neurol. Sci., 17, pp. 149-166, (1972)

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