Purpose

Multiple factors influence intrauterine growth and lead to low birth sizes. The impact of genetic alterations on both pre- and post-natal growth is still largely unknown. The aim of this study was to investigate the prevalence of CNVs in an Italian cohort of SGA children with persistent short stature and complex clinical phenotype. rhGH treatment efficacy was evaluated according to the different genotypes.

Subjects and methods

Twenty-four SGA children (10F/14M) with persistent short stature associated with dysmorphic features and/or developmental delay underwent CNV evaluation.

Results

CNVs were present in 14/24 (58%) SGA children. Six patients had a microdeletion involving the following regions: 3q24q25.1, 8p21.2p12, 15q26, 19q13.11, 20q11.21q12, 22q11.2. In three females, the same microdeletion involving 17p13.3 region was identified. In two different patients, two microduplications involving 10q21.3 and Xp11.3 region were observed. A further female patient showed both an 11q12.1 and an Xq27.1 microduplication, inherited from her mother and from her father, respectively. In a boy, the presence of a 12p13.33 microdeletion and a 19q13.43 microduplication was found. GH treatment efficacy, expressed by height gain and height velocity in the first 12 months of therapy, was similar in subjects with and without CNVs.

Conclusions

These results show that pathogenic CNVs are common in SGA children with short stature associated with additional clinical features. Interestingly, the involvement of 17p13.3 region occurs with a relative high frequency, suggesting that genes located in this region could play a key role in pre- and post-natal growth. rhGH therapy has similar efficacy in the short term whether CNVs are present or not.

中文翻译：

---

在意大利出生小于胎龄儿 (SGA) 的儿童队列中拷贝数变异 (CNV) 的患病率和 rhGH 治疗效果与复杂的临床表型相关的持续身材矮小

目的

多种因素影响宫内生长并导致低出生体型。遗传改变对产前和产后生长的影响仍然很大程度上未知。本研究的目的是调查意大利 SGA 儿童队列中 CNVs 的患病率，这些儿童具有持续的身材矮小和复杂的临床表型。根据不同基因型评估rhGH治疗效果。

主题和方法

24 名 SGA 儿童 (10F/14M) 与畸形特征和/或发育迟缓相关的持续身材矮小接受了 CNV 评估。

结果

CNVs 存在于 14/24 (58%) SGA 儿童中。6 名患者出现涉及以下区域的微缺失：3q24q25.1、8p21.2p12、15q26、19q13.11、20q11.21q12、22q11.2。在三名女性中，确定了涉及 17p13.3 区域的相同微缺失。在两名不同的患者中，观察到涉及 10q21.3 和 Xp11.3 区域的两个微重复。另一名女性患者显示出 11q12.1 和 Xq27.1 微重复，分别从她的母亲和她的父亲那里继承。在一个男孩中，发现了一个 12p13.33 微缺失和一个 19q13.43 微重复。以治疗前 12 个月的身高增长和身高增长速度表示的 GH 治疗效果在有和没有 CNV 的受试者中相似。

结论

这些结果表明，致病性 CNV 在与其他临床特征相关的身材矮小 SGA 儿童中很常见。有趣的是，17p13.3 区域的参与频率相对较高，表明位于该区域的基因可能在产前和产后生长中起关键作用。无论 CNV 是否存在，rhGH 疗法在短期内都具有相似的疗效。