Department of Endocrinology, Genetics and Metabolism, Affiliated Hospital of Jining Medical University, Jining Medical University, 89 Guhuai Road, Jining, Shandong 272029, PR China; Chinese Research Center for Behavior Medicine in Growth and Development, 89 Guhuai Road, Jining, Shandong 272029, PR China.
Medical Research Center, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, Shandong 272029, PR China.
Clin Chim Acta. 2024 Feb 1;554:117779. doi: 10.1016/j.cca.2024.117779. Epub 2024 Jan 12.
Significant differences have been observed in the efficacy of recombinant human growth hormone (rhGH) treatment for short children. The present study aimed to identify the genetic etiology of short stature and to assess the role of molecular diagnosis in predicting responses to rhGH treatment.
A total of 407 short children were included in the present study, 226 of whom received rhGH treatment. Whole-exome sequencing (WES) was conducted on short children to identify the underlying genetic etiology. Correlations between molecular diagnosis and the efficacy of rhGH treatment were examined.
Pathogenic or likely pathogenic mutations were identified in 86 of the 407 patients (21.1%), including 36 (41.9%) novel variants. Among the multiple pathways affecting short stature, genes involved in fundamental cellular processes (38.7%) play a larger role, especially the RAS-MAPK pathway. In general, patients without pathogenic mutations responded better to rhGH than those with mutations. Furthermore, patients with hormone signaling pathway mutations had a better response to rhGH, while those with paracrine factor mutations had a worse response to rhGH.
This study highlights the utility of WES in identifying genetic etiology in children with short stature. Identifying likely causal mutations is an important factor in predicting rhGH response.
重组人生长激素（rhGH）治疗身材矮小儿童的疗效存在显著差异。本研究旨在确定矮小症的遗传病因，并评估分子诊断在预测 rhGH 治疗反应中的作用。
本研究共纳入 407 名身材矮小的儿童，其中 226 名接受 rhGH 治疗。对身材矮小的儿童进行全外显子组测序（WES），以确定潜在的遗传病因。检查了分子诊断与 rhGH 治疗疗效之间的相关性。
在 407 名患者中，有 86 名（21.1%）发现了致病性或可能致病性突变，其中包括 36 个（41.9%）新变异。在影响身材矮小的多个途径中，参与基本细胞过程的基因（38.7%）发挥了更大的作用，尤其是 RAS-MAPK 途径。一般来说，无致病性突变的患者对 rhGH 的反应优于有突变的患者。此外，激素信号通路突变的患者对 rhGH 的反应较好，而旁分泌因子突变的患者对 rhGH 的反应较差。
本研究强调了 WES 在确定身材矮小儿童遗传病因中的作用。确定可能的因果突变是预测 rhGH 反应的重要因素。
