Huang Yiyun, Peng Yan, Li Chuan, Xie Bobo, Wei Xianda, Gui Baoheng, Meng Juan, Chen Shaoke, Fan Xin
Department of Pediatrics, The Second Affiliated Hospital of Guangxi Medical University, No.166, Daxuedong Road, Nanning, 530007, Guangxi Zhuang Autonomous Region, China.
Center for Medical Genetics and Genomics, The Second Affiliated Hospital of Guangxi Medical University, No.166, Daxuedong Road, Nanning, 530007, Guangxi Zhuang Autonomous Region, China.
Sci Rep. 2025 Jul 1;15(1):20717. doi: 10.1038/s41598-025-07570-w.
This study aimed to explore the genotype-phenotype correlations in individuals with Genetic Skeletal Disorders (GSD), evaluate the efficacy of recombinant human Growth Hormone (rhGH) therapy. The retrospective analysis of the medical records of 80 pediatric patients with GSD diagnosed via whole-exome sequencing was conducted. The therapeutic effects of rhGH treatment were analyzed in 30 of these patients who received rhGH therapy. The study included 80 GSD patients, diagnosed at a median age of 4.88 years, with a median height standard deviation score (Ht-SDS) of - 3.58. The most common clinical manifestations included skeletal deformities (87.5%), short stature (81.3%), and distinctive facial features (including triangular face, abnormality of the philtrum, abnormality of the forehead, etc.) (65.0%). A total of 33 pathogenic genes associated with 20 groups of GSD were identified. The most common groups are Type II collagenopathies (related to the COL2A1 gene) (12/80, 15.0%) and the FGFR3-related chondrodysplasia group (12/80, 15.0%). Those with pathogenic genes linked to Fundamental Cellular Processes had more severe short stature and prenatal phenotypes. Thirty patients received rhGH treatment for a median of 2.25 years (0.33-8.92), showing Ht-SDS increases of 0.66 ± 0.42 and 0.84 ± 0.52, after one and two years, respectively (p < 0.001). Eight untreated patients had an average Ht-SDS decrease of - 0.46 ± 0.55. In this cohort, pediatric GSD patients predominantly presented with short stature, skeletal deformities, and distinctive facial features (including triangular face, abnormality of the philtrum, abnormality of the forehead, etc.), indicating a genotype-phenotype correlation. Compared to untreated GSD patients, those receiving rhGH treatment demonstrated varying degrees of height improvement, however, the long-term efficacy of this treatment warrants further investigation.
本研究旨在探讨遗传性骨骼疾病（GSD）患者的基因型与表型的相关性，评估重组人生长激素（rhGH）治疗的疗效。对80例通过全外显子测序诊断为GSD的儿科患者的病历进行回顾性分析。对其中30例接受rhGH治疗的患者的治疗效果进行分析。该研究纳入了80例GSD患者，诊断时的中位年龄为4.88岁，中位身高标准差评分（Ht-SDS）为-3.58。最常见的临床表现包括骨骼畸形（87.5%）、身材矮小（81.3%）和独特的面部特征（包括三角脸、人中异常、额头异常等）（65.0%）。共鉴定出与20组GSD相关的33个致病基因。最常见的组是II型胶原病（与COL2A1基因相关）（12/80，15.0%）和FGFR3相关的软骨发育异常组（12/80，15.0%）。那些与基本细胞过程相关的致病基因的患者身材矮小和产前表型更为严重。30例患者接受rhGH治疗的中位时间为2.25年（0.33 - 8.92），治疗1年和2年后，Ht-SDS分别增加0.66±0.42和0.84±0.52（p<0.001）。8例未治疗的患者Ht-SDS平均下降-0.46±0.55。在该队列中，儿科GSD患者主要表现为身材矮小、骨骼畸形和独特的面部特征（包括三角脸、人中异常、额头异常等），表明存在基因型与表型的相关性。与未治疗的GSD患者相比，接受rhGH治疗的患者身高有不同程度的改善，然而，这种治疗的长期疗效有待进一步研究。
