Huang Yanru, Zhou Yixi, Zhang Lutan, Shen Ye, Yao Xingmei, Xie Jieqiong, Mei Libin, Ge Yunsheng
Department of Central Laboratory, Fujian Key Clinical Specialty of Laboratory Medicine, Department of Obstetrics and Gynecology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian 361003, P.R. China.
Department of Central Laboratory, Fujian Key Clinical Specialty of Laboratory Medicine, Department of Obstetrics and Gynecology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian 361003, P.R. China.
Mol Med Rep. 2025 Aug;32(2). doi: 10.3892/mmr.2025.13582. Epub 2025 May 30.
Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by high genetic and phenotypic heterogeneity. Notably, 90% of cases of OI are caused by pathogenic variants in the and genes, with those in being the most common. The present study aimed to investigate the genetic etiology of OI in a family and the pathogenicity of the splice‑site variant. Whole‑exome sequencing was performed for the proband and Sanger sequencing was performed for all family members to validate the results. Reverse transcription (RT)‑PCR on lymphocyte strains was performed on the proband and an age‑matched control, and minigene experiments were performed to verify the splicing patterns. A heterozygous variant, c.3531+1G>T, was detected in in all patients in the family. RT‑PCR showed an increase in abnormal transcript expression and a decrease in normal transcript expression in the proband. Minigene splicing assays revealed that the mutant gene exhibited four splicing patterns, whereas the normal gene exhibited three splicing patterns. This finding indicated that the c.3531+1G>T variant site affected intron 47 splicing. To the best of our knowledge, this variant was first reported in the Palestinian population, whereas the present study is the first to report this variant in the Chinese population and to clarify the effect of this variant. The results expand the spectrum of pathogenic variants associated with OI.
成骨不全症（OI）是一种结缔组织疾病，其特征是具有高度的遗传和表型异质性。值得注意的是，90%的OI病例是由 和 基因的致病变异引起的，其中 基因的变异最为常见。本研究旨在调查一个家庭中OI的遗传病因以及剪接位点变异的致病性。对先证者进行了全外显子组测序，并对所有家庭成员进行了桑格测序以验证结果。对先证者和年龄匹配的对照进行了淋巴细胞株的逆转录（RT）-PCR，并进行了小基因实验以验证剪接模式。在该家庭的所有患者中，在 基因中检测到一个杂合变异，c.3531+1G>T。RT-PCR显示先证者中异常转录本表达增加，正常转录本表达减少。小基因剪接分析表明，突变基因表现出四种剪接模式，而正常基因表现出三种剪接模式。这一发现表明c.3531+1G>T变异位点影响内含子47的剪接。据我们所知，该变异首次在巴勒斯坦人群中报道，而本研究是首次在中国人群中报道该变异并阐明其影响。这些结果扩展了与OI相关的致病变异谱。
