Developmental Trajectory of Height, Weight, and BMI in Children and Adolescents at Risk for Huntington's Disease: Effect of mHTT on Growth.
Developmental Trajectory of Height, Weight, and BMI in Children and Adolescents at Risk for Huntington's Disease: Effect of mHTT on Growth.
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DOI：
10.3233/jhd-200407
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Nopoulos P
中科院分区：
文献类型：
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作者：
Tereshchenko A;van der Plas E;Mathews KD;Epping E;Conrad AL;Langbehn DR;Nopoulos P
导致亨廷顿氏病（HD）的基因（亨廷顿蛋白或HTT）对发育至关重要，并在整个大脑和身体终身表达。突变形式（mHTT）可能影响生长和发育。确定mHTT对儿童和青少年mHTT携带者与对照同龄人之间的人类生长指标（包括身高、体重和体重指数（BMI））的影响。有HD风险的6-18岁儿童（n =186）入组KidsHD研究。 仅出于研究目的，进行基因检测以将参与者分类为基因扩增（GE = 78）或基因非扩增（GNE = 108）。 结果测量包括身高、体重和体重指数（BMI）。使用混合模型来确定BMI、身高和体重的非线性年龄趋势在组间是否存在差异。在BMI的轨迹中观察到了差异，其中GE组在青春期后期达到平台期，没有进一步增加，而GNE组几乎呈线性增加。有一个显着的性别互动模式，GE男性高于GNE男性在青春期，在类似的重量存在。相比之下，GE女性在青春期的体重明显低于GNE女性，身高相似。在HD发病前几十年，mHTT的儿童和青少年携带者的生长指标异常。虽然还需要进一步的研究来复制，但目前的研究结果表明，发育畸变可能是系统性的，是疾病病理学的重要组成部分。
The gene (Huntingtin or HTT) causing Huntington’s disease (HD) is vital for development and is expressed throughout the brain and body lifelong. The mutant form (mHTT) may influence growth and development. To determine the impact of mHTT on human measures of growth, including height, weight, and body mass index (BMI), between child and adolescent carriers of mHTT and control peers. Children ages 6–18 years of age (n = 186) at risk for HD were enrolled in the KidsHD study. For research purposes only, genetic testing was performed to classify participants as Gene-Expanded (GE = 78) or as Gene Non-Expanded (GNE = 108). Outcome measures included height, weight, and body mass index (BMI). Mixed models were used to determine if non-linear age trends differed between groups for BMI, height, and weight. Differences were seen in the trajectory of BMI in which the GE group reached a plateau in late adolescence with no further increase, compared with a nearly linear increase in the GNE group. There was a significant sex interaction pattern where GE males were taller than GNE males in adolescence, in the presence of similar weight. In contrast, GE females weighed significantly less than their GNE counterparts in adolescence, in the presence of similar height. Measures of growth are abnormal in child and adolescent carriers of mHTT, decades before HD onset. Although further studies are needed for replication, the current findings suggest that developmental aberrations may be systemic and a vital part of disease pathology.