Clinical Institute of Special Laboratory Diagnostics, University Children's Hospital, UMC, 1000 Ljubljana, Slovenia.
Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, UMC, 1000 Ljubljana, Slovenia.
Genes (Basel). 2021 Sep 29;12(10):1546. doi: 10.3390/genes12101546.
Short stature is a common growth disorder defined as a body height two standard deviations (SD) or more below the mean for a given age, gender, and population. A large part of the cases remains unexplained and is referred to as having idiopathic short stature (ISS). One of the leading genetic causes of short stature is variants of short stature homeobox-containing gene () and is considered to be responsible for 2-15% of ISS. We aimed to analyse the regulatory and coding region of in Slovenian children and young adults with ISS and to investigate the pathogenicity of detected variants. Our cohort included 75 children and young adults with ISS. Multiplex ligation-dependent probe amplification (MLPA) was performed in all participants for the detection of larger copy number variations (CNVs). Sanger sequencing was undertaken for the detection of point variants, small deletions, and insertions. A total of one deletion and two duplications were discovered using the MLPA technique. Only one of these four variants was identified as disease-causing and occurred in one individual, which represents 1.3% of the cohort. With Sanger sequencing, two variants were discovered, but none of them appeared to have a pathogenic effect on height. According to the results, in the Slovenian population of children and young adults with ISS, deficiency is less frequent than expected considering existing data from other populations.
身材矮小是一种常见的生长障碍，定义为身高比特定年龄、性别和人群的平均值低两个标准差（SD）或更多。很大一部分病例原因不明，被称为特发性身材矮小（ISS）。导致身材矮小的主要遗传原因之一是短身高同源盒基因（）的变异，据认为其占 ISS 的 2-15%。我们旨在分析斯洛文尼亚 ISS 儿童和青年的 基因的调控和编码区，并研究检测到的变异的致病性。我们的队列包括 75 名 ISS 儿童和青年。所有参与者均进行多重连接依赖性探针扩增（MLPA）以检测较大的拷贝数变异（CNV）。进行 Sanger 测序以检测点变异、小缺失和插入。使用 MLPA 技术发现了一个缺失和两个重复。这四个变体中只有一个被确定为致病性变体，发生在一个个体中，占队列的 1.3%。通过 Sanger 测序发现了两个变体，但它们都没有对身高产生致病性影响。根据结果，在斯洛文尼亚 ISS 儿童和青年人群中，与其他人群的现有数据相比， 缺乏的频率低于预期。
