携带低外显率等位基因的亨廷顿病患者的发病年龄。
Age of Onset of Huntington's Disease in Carriers of Reduced Penetrance Alleles.
机构信息
Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York, USA.
Department of Psychiatry, Columbia University Medical Center, New York, New York, USA.
出版信息
Mov Disord. 2021 Dec;36(12):2958-2961. doi: 10.1002/mds.28789. Epub 2021 Sep 18.
BACKGROUND
Age of manifest Huntington's disease (HD) onset correlates with number of CAG repeats in the huntingtin gene. Little is known about onset with 36 to 39 repeats, the "reduced penetrance" (RP) range.
OBJECTIVES
We provide allele-specific estimates of HD penetrance (diagnostic confidence level of 4) for RP allele carriers.
METHODS
We analyzed 431 pre-manifest RP allele carriers from Enroll-HD, the largest prospective observational HD study. Cumulative penetrance (CP) was estimated from Kaplan-Meier curves.
RESULTS
No one with 36 repeats (n = 25) phenoconverted. CP for 38 repeats (n = 120) was 32% (95% confidence interval [CI] 0%-55%) and 51% (CI, 10%-73%) by ages 70 and 75, respectively, and 68% (CI, 46%-81%) and 81% (CI, 58%-92%) by ages 70 and 75 for 39 repeats (n = 253). CP was not estimable at those ages for 37 repeats (n = 33).
CONCLUSIONS
Differences by RP-range repeat length did not reach significance with a 3-year median follow-up duration among censored individuals. © 2021 International Parkinson and Movement Disorder Society.
背景
亨廷顿病（HD）明显发病年龄与亨廷顿基因中的 CAG 重复次数相关。对于 36 到 39 个重复的发病年龄，即“低外显率”（RP）范围，人们知之甚少。
目的
我们提供了针对 RP 等位基因携带者的 HD 外显率（诊断置信度为 4）的等位基因特异性估计。
方法
我们分析了来自 Enroll-HD 的 431 名前 RP 等位基因携带者，这是最大的前瞻性观察性 HD 研究。累积外显率（CP）是从 Kaplan-Meier 曲线估计得出的。
结果
没有一个 36 个重复的人出现表型转化（n=25）。38 个重复的 CP 在 70 岁时分别为 32%（95%置信区间 [CI] 0%-55%）和 51%（CI，10%-73%），在 75 岁时分别为 68%（CI，46%-81%）和 81%（CI，58%-92%），而 39 个重复的 CP 在 70 岁和 75 岁时无法估计（n=253）。37 个重复的 CP 在这些年龄也无法估计（n=33）。
结论
在截尾个体的中位随访 3 年期间，RP 范围重复长度的差异没有达到统计学意义。© 2021 国际帕金森病和运动障碍学会。
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