Short stature is defined as a body height below the third percentile, based on chronological age, or 2 standard deviations (SD) below the national height standard. The prevalence of short stature is around 2% of children worldwide. Several gene deficiencies have been associated with the etiology of short stature. The SHOX is an important candidate gene for short stature, as its haploinsufficiency underlies syndromic and non-syndromic short stature. Partial and complete duplications of SHOX have been reported in patients with short stature. Proper genetic diagnosis of these children allows for appropriate therapeutic approaches to be administered. Since copy number variation (CNV) is a possible mechanism of interhuman variability and pathogenic disease, the multiplex ligation-dependent probe amplification technique (MLPA) can be used as an initial screening technique. Cartilage tissue expresses specific microRNAs (miRNAs), which play an essential role in the regulation of chondrocyte proliferation and differentiation during growth plate development. We aimed to assess the SHOX/PAR1 region using CNV profiling for non-syndromic short stature in Egyptian children with and without growth hormone deficiency using the MLPA technique and expression profiling of miR-1, miR-15a, and miR-140 using quantitative real-time polymerase chain reaction (qRT-PCR) in a group of Egyptian children with non-syndromic short stature. Of the fifty cases included in this study, different CNVs were detected in ten children (20%), in/outside the SHOX region. Moreover, in children with short stature, the expression level of miRNA-140 was significantly different from that of healthy controls. This is one of the first studies that have assessed CNVs in the SHOX/PAR1 region in a group of Egyptian children with short stature. MLPA analysis of SHOX/PAR1 identified different CNVs in children with non-syndromic short stature, suggesting that the MLPA should be used as an initial screening technique in short children, as proper genetic diagnosis of these children leads to implementation of the appropriate therapeutic approach. Alterations in the levels of miRNA-140 in children with short stature suggest that changes in the expression levels of this miRNA are associated with the pathogenesis of short stature.

中文翻译：

---

使用 MLPA 和 miRNA 表达谱在一组非综合征性身材矮小的埃及儿童中筛选 SHOX/PAR1 区域

身材矮小被定义为基于实际年龄低于第三个百分位数的身高，或低于国家身高标准 2 个标准差 (SD)。全世界儿童中身材矮小的患病率约为 2%。一些基因缺陷与身材矮小的病因有关。SHOX 是身材矮小的重要候选基因，因为其单倍体不足是综合征性和非综合征性身材矮小的基础。据报道，身材矮小患者会出现部分和完全重复的 SHOX。对这些儿童进行适当的基因诊断可以采取适当的治疗方法。由于拷贝数变异 (CNV) 是人类变异和致病疾病的可能机制，多重连接依赖性探针扩增技术 (MLPA) 可用作初步筛选技术。软骨组织表达特定的微小 RNA (miRNA)，其在生长板发育过程中调节软骨细胞增殖和分化中发挥重要作用。我们的目的是使用 CNV 分析评估 SHOX/PAR1 区域，使用 MLPA 技术对有和没有生长激素缺乏的埃及儿童的非综合征性身材矮小进行评估，并使用定量真实数据对 miR-1、miR-15a 和 miR-140 进行表达分析。 -时间聚合酶链反应 (qRT-PCR) 在一组非综合征性身材矮小的埃及儿童中进行。在本研究中包括的 50 个病例中，在 SHOX 区域内/外的 10 个儿童 (20%) 中检测到不同的 CNV。此外，对于身材矮小的儿童，miRNA-140 的表达水平与健康对照显着不同。这是对一组身材矮小的埃及儿童的 SHOX/PAR1 区域的 CNV 进行评估的首批研究之一。SHOX/PAR1 的 MLPA 分析在非综合征性矮小儿童中鉴定出不同的 CNV，这表明 MLPA 应用作矮小儿童的初步筛查技术，因为对这些儿童进行正确的基因诊断会导致实施适当的治疗方法。矮小儿 miRNA-140 水平的变化表明该 miRNA 表达水平的变化与矮小症的发病机制有关。这是对一组身材矮小的埃及儿童的 SHOX/PAR1 区域的 CNV 进行评估的首批研究之一。SHOX/PAR1 的 MLPA 分析在非综合征性矮小儿童中鉴定出不同的 CNV，这表明 MLPA 应用作矮小儿童的初步筛查技术，因为对这些儿童进行正确的基因诊断会导致实施适当的治疗方法。矮小儿 miRNA-140 水平的变化表明该 miRNA 表达水平的变化与矮小症的发病机制有关。这是对一组身材矮小的埃及儿童的 SHOX/PAR1 区域的 CNV 进行评估的首批研究之一。SHOX/PAR1 的 MLPA 分析在非综合征性矮小儿童中鉴定出不同的 CNV，这表明 MLPA 应用作矮小儿童的初步筛查技术，因为对这些儿童进行正确的基因诊断会导致实施适当的治疗方法。矮小儿 miRNA-140 水平的变化表明该 miRNA 表达水平的变化与矮小症的发病机制有关。建议 MLPA 应用作矮小儿童的初步筛查技术，因为对这些儿童进行适当的基因诊断会导致实施适当的治疗方法。矮小儿 miRNA-140 水平的变化表明该 miRNA 表达水平的变化与矮小症的发病机制有关。建议 MLPA 应用作矮小儿童的初步筛查技术，因为对这些儿童进行适当的基因诊断会导致实施适当的治疗方法。矮小儿 miRNA-140 水平的变化表明该 miRNA 表达水平的变化与矮小症的发病机制有关。