MOLECULAR-FEATURES OF THE CAG REPEATS AND CLINICAL MANIFESTATION OF MACHADO-JOSEPH DISEASE

被引：165

作者：

MARUYAMA, H

NAKAMURA, S

MATSUYAMA, Z

SAKAI, T

DOYU, M

SOBUE, G

SETO, M

TSUJIHATA, M

OHI, T

NISHIO, T

SUNOHARA, N

TAKAHASHI, R

HAYASHI, M

NISHINO, I

OHTAKE, T

ODA, T

NISHIMURA, M

SAIDA, T

MATSUMOTO, H

BABA, M

KAWAGUCHI, Y

KAKIZUKA, A

KAWAKAMI, H

机构：

[1] HIROSHIMA UNIV,SCH MED,DEPT INTERNAL MED 3,HIROSHIMA 734,JAPAN

[2] NATL CHIKUGO HOSP,DEPT NEUROL,FUKUOKA 833,JAPAN

[3] AICHI MED UNIV,DEPT INTERNAL MED 4,DIV NEUROL,NAGAKUTE,AICHI 48011,JAPAN

[4] NAGASAKI KITA HOSP,DIV NEUROL,NAGASAKI 852,JAPAN

[5] MIYAZAKI MED COLL,DEPT INTERNAL MED 3,MIYAZAKI 89916,JAPAN

[6] NCNP,NATL CTR HOSP,DEPT NEUROL,KODAIRA,TOKYO 187,JAPAN

[7] TOKYO METROPOLITAN INST NEUROSCI,DEPT NEUROL,TOKYO 183,JAPAN

[8] TOKYO METROPOLITAN NEUROL HOSP,DEPT NEUROL,TOKYO,JAPAN

[9] NATL SHIMOFUSA SANATORIUM,DEPT NEUROPSYCHIAT,CHIBA 266,JAPAN

[10] UTANO NATL HOSP,DEPT NEUROL,KYOTO 616,JAPAN

[11] UTANO NATL HOSP,CLIN RES CTR,KYOTO 616,JAPAN

[12] SAPPORO MED UNIV,DEPT NEUROL,SAPPORO,HOKKAIDO 060,JAPAN

[13] HIROSAKI UNIV,SCH MED,DEPT NEUROL,HIROSAKI,AOMORI 036,JAPAN

[14] KYOTO UNIV,FAC MED,DEPT PHARMACOL,KYOTO 60601,JAPAN

来源：

HUMAN MOLECULAR GENETICS | 1995年 / 4卷 / 05期

关键词：

D O I：

10.1093/hmg/4.5.807

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：

Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration mapped to chromosome 14q32.1. The CAG expansions of the MJD1 gene was identified as the cause of the disease, We have analyzed 90 MJD individuals from 62 independent MJD families and found that the MJD1 repeat length is inversely correlated with the age of onset (r = -0.87). The MJD chromosomes contained 61-84 repeat units, whereas normal chromosomes displayed 14-34 repeats. In the normal chromosomes, 14 repeat units were the most common and the shortest. In association with the clinical anticipation of the disease, a parent-child analysis showed the unidirectional expansion of CAG repeats and no case of diminution in the affected family, The differences in CAG repeat length between parent and child and between siblings are greater in paternal transmission than in maternal transmission. Detailed analysis revealed that a large degree of expansion was associated with a shorter length of MJD1 gene in paternal transmission, On the other hand, the increments of increase were similar for shorter and longer expansion in maternal transmission, Among the three clinical subtypes, type I of MJD, with dystonia, showed a larger degree of expansion in CAG repeats of the gene and younger ages of onset than the other types.

引用

页码：807 / 812

页数：6

共 22 条

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