Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats.
Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats.
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发表时间：
1996-07
影响因子：
9.8
通讯作者：
D. Rubinsztein;J. Leggo;Rhian;Coles;E. Almqvist;V. Biancalana;J. Cassiman;K. Chotai;Margaret;Connarty;D. Craufurd;A. Curtis;D. Curtis;M. Davidson;C. Dodé;A. Dodge;M. Frontali;N. Ranen;C. Stine;M. Sherr;M. Abbott;M. Franz;C. Graham;P. Harper;C. John;Hedreen;A. Jackson;M. Losekoot;J. MacMillan;P. Morrison;Y. Trottier;A. Novelletto;S. Simpson;'. J. Theilmann;L. Joanne;Whittaker;S. Folstein;C. Ross;M. Hayden
中科院分区：
文献类型：
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作者：
D. Rubinsztein;J. Leggo;Rhian;Coles;E. Almqvist;V. Biancalana;J. Cassiman;K. Chotai;Margaret;Connarty;D. Craufurd;A. Curtis;D. Curtis;M. Davidson;C. Dodé;A. Dodge;M. Frontali;N. Ranen;C. Stine;M. Sherr;M. Abbott;M. Franz;C. Graham;P. Harper;C. John;Hedreen;A. Jackson;M. Losekoot;J. MacMillan;P. Morrison;Y. Trottier;A. Novelletto;S. Simpson;'. J. Theilmann;L. Joanne;Whittaker;S. Folstein;C. Ross;M. Hayden
IT-15基因中CAG的异常扩张与亨廷顿病(HD)有关。在诊断环境中，有必要确定正常染色体和HD相关染色体上CAG大小范围的界限。大多数定义正常和病理大小范围界限的大型分析都使用了聚合酶链式反应分析，包括CAG重复序列和被认为是不变的CCG重复序列。许多这些实验发现，正常大小和疾病大小范围之间存在重叠。随后发现，CCG重复序列有8个三核苷酸长度的差异，这表明应该用排除CCG多态的分析来重新评估正常和疾病大小范围的界限。由于有30到40个重复序列的患者很少见，因此成立了一个联盟来收集这些个体。在剑桥大学，所有178个样本都被重新分析，使用的是针对CAG重复的分析方法。我们已经优化了CAG重复序列可靠大小的方法，并展示了使用同时包括CAG和CCG多态的PCR分析的危险的案例。7名HD患者有36个重复，这证实了该等位基因与疾病相关。无明显HD症状或体征的个体重复36次(年龄74、78、79和87岁)，37次(69岁)，38次(69岁和90岁)，39次(67、90和95岁)。本系列中的一个特殊病例的详细病历将被呈现：一位95岁的男性，有39次重复，他没有HD的经典特征。一些有36-39个重复序列的个体明显健康地存活到老年，这表明HD突变可能并不总是完全穿透的。
Abnormal CAG expansions in the IT-15 gene are associated with Huntington disease (HD). In the diagnostic setting it is necessary to define the limits of the CAG size ranges on normal and HD-associated chromosomes. Most large analyses that defined the limits of the normal and pathological size ranges employed PCR assays, which included the CAG repeats and a CCG repeat tract that was thought to be invariant. Many of these experiments found an overlap between the normal and disease size ranges. Subsequent findings that the CCG repeats vary by 8 trinucleotide lengths suggested that the limits of the normal and disease size ranges should be reevaluated with assays that exclude the CCG polymorphism. Since patients with between 30 and 40 repeats are rare, a consortium was assembled to collect such individuals. All 178 samples were reanalyzed in Cambridge by using assays specific for the CAG repeats. We have optimized methods for reliable sizing of CAG repeats and show cases that demonstrate the dangers of using PCR assays that include both the CAG and CCG polymorphisms. Seven HD patients had 36 repeats, which confirms that this allele is associated with disease. Individuals without apparent symptoms or signs of HD were found at 36 repeats (aged 74, 78, 79, and 87 years), 37 repeats (aged 69 years), 38 repeats (aged 69 and 90 years), and 39 repeats (aged 67, 90, and 95 years). The detailed case histories of an exceptional case from this series will be presented: a 95-year-old man with 39 repeats who did not have classical features of HD. The apparently healthy survival into old age of some individuals with 36-39 repeats suggests that the HD mutation may not always be fully penetrant.