Liang Jie, Han Yu, Tao Huimin, Wang Xuezhen, Zhang Bei, Wu Jiebin, Zhai Jingfang
Xuzhou Clinical College of Xuzhou Medical University, Xuzhou Central Hospital, Xuzhou, China.
Department of Prenatal Diagnosis Medical Center, Xuzhou Central Hospital, Xuzhou, Jiangsu, China.
Medicine (Baltimore). 2024 Dec 20;103(51):e41000. doi: 10.1097/MD.0000000000041000.
The aim of this study is to investigate the de novo mutation and clinical features of latent transforming growth factor-beta-binding protein 3 (LTBP3) gene-associated geleophysic dysplasia 3, and possible mechanisms of action.
A nonconsanguineous couple was recruited for this study due to the presence of intrauterine growth restriction. The pregnant woman and her elder daughter presented with skeletal abnormalities with diabetes. The pregnant woman underwent amniocentesis for cytogenetic analysis and copy number variation sequencing. Furthermore, we employed a combination of pedigree whole exome sequencing and bioinformatics analysis to predict the effects of mutations.
The results of karyotyping and copy number variation sequencing were normal. And the whole exome sequencing results indicated that the family carried a de novo mutation c.852_853insAGG (p.L284_P285insR) in the LTBP3 gene (NM_001130144.3) inherited from the mother. The results of bioinformatics prediction demonstrated the mutation influenced the stability of the LTBP3 gene, thereby enhanced the transforming growth factor β signaling pathways.
The couple terminated the pregnancy after comprehensive consideration.
A de novo non-frameshift mutation of the LTBP3 gene might enhance the transforming growth factor β signaling pathways, thereby leading to geleophysic dysplasia 3.
As a rare multi-system musculoskeletal disorder, geleophysic dysplasia 3 necessitates early prenatal diagnosis and multidisciplinary consultation in order to facilitate further diagnosis and evaluation of the patient and the fetus.
本研究旨在调查潜伏转化生长因子β结合蛋白3（LTBP3）基因相关的格利菲斯发育不良3型的新生突变和临床特征，以及可能的作用机制。
因存在宫内生长受限，招募了一对非近亲夫妇参与本研究。该孕妇及其长女患有骨骼异常并伴有糖尿病。孕妇接受了羊水穿刺术进行细胞遗传学分析和拷贝数变异测序。此外，我们采用家系全外显子组测序和生物信息学分析相结合的方法来预测突变的影响。
核型分析和拷贝数变异测序结果均正常。全外显子组测序结果表明，该家系携带一个从母亲遗传而来的LTBP3基因（NM_001130144.3）的新生突变c.852_853insAGG（p.L284_P285insR）。生物信息学预测结果表明，该突变影响了LTBP3基因的稳定性，从而增强了转化生长因子β信号通路。
这对夫妇经过综合考虑后终止了妊娠。
LTBP3基因的新生非移码突变可能增强转化生长因子β信号通路，从而导致格利菲斯发育不良3型。
作为一种罕见的多系统肌肉骨骼疾病，格利菲斯发育不良3型需要早期产前诊断和多学科会诊，以便对患者和胎儿进行进一步的诊断和评估。
