Abstract

Background

Hereditary transthyretin amyloidosis (ATTRV30M) is a rare disease caused by amyloid deposition and characterized by a heterogeneous presentation. Anticipation (AC) is described as the decrease in age at onset (AO) within each generation. Our aim was to study AC in a large number of ATTRV30M kindred from Majorca (Spain), and gain further insight into parent-of-origin effects.

Methods

In a cohort of 262 subjects with ATTRV30M amyloidosis belonging to 51 families, we found 37 affected pairs. AO is defined as the age at the first symptom and AC (parent’s age at disease onset minus that of the offspring) were calculated. Chi-square test, independent t-test and paired t-test were used for comparisons between groups. Association between AO of parents and offsprings were assessed by Pearson’s correlation coefficient.

Results

Offspring mean AO was 16 years lower than that of the parents (p < .001) regardless of the sex of the parents and the offspring. AC occurred in 31 out of the 37 pairs, with no differences related to the sex of parents or offspring. There was a moderate correlation (r = 0.49; p < .001) between AO of the parents and that of the offsprings.

Conclusion

AC was no uncommon in our cohort, and AO tended to decrease in successive generations.

中文翻译：

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对来自马略卡岛群的遗传性 ATTRV30M 淀粉样变性家族中发病年龄的预测。

摘要

背景

遗传性转甲状腺素蛋白淀粉样变性 (ATTRV30M) 是一种由淀粉样蛋白沉积引起的罕见疾病，其特征是表现出异质性。预期 (AC) 被描述为每一代内发病年龄 (AO) 的减少。我们的目标是在来自马略卡岛（西班牙）的大量 ATTRV30M 亲属中研究 AC，并进一步了解亲本效应。

方法

在属于 51 个家庭的 262 名 ATTRV30M 淀粉样变性受试者的队列中，我们发现了 37 对受影响的患者。AO 定义为首次出现症状时的年龄，并计算出 AC（父母发病时的年龄减去后代的年龄）。卡方检验、独立t检验和配对t检验用于组间比较。父母与后代AO之间的关联通过Pearson相关系数进行评估。

结果

 无论父母和后代的性别如何，后代的平均 AO 都比父母的低 16 年 ( p < .001)。AC 发生在 37 对中的 31 对中，与父母或后代的性别无关。 父母的 AO 和后代的 AO 之间存在中等相关性 ( r  = 0.49; p < .001)。

结论

AC 在我们的队列中并不少见，并且 AO 在连续几代中趋于减少。