Janchevska Aleksandra, Krstevska-Konstantinova Marina, Pfäffle Heike, Schlicke Marina, Laban Nevenka, Tasic Velibor, Gucev Zoran, Mironska Kristina, Dimovski Aleksandar, Kratzsch Jürgen, Klammt Jürgen, Pfäffle Roland
Medical Faculty, Ss. Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia.
University of Leipzig, Leipzig, Germany.
Open Access Maced J Med Sci. 2018 Nov 10;6(11):2040-2044. doi: 10.3889/oamjms.2018.416. eCollection 2018 Nov 25.
Small for gestational age (SGA)-born children are a heterogeneous group with few genetic causes reported. Genetic alterations in the IGF1 receptor (IGF1R) are found in some SGA children.
To investigate whether alterations in gene are present in SGA born children.
We analysed 64 children born SGA who stayed short (mean -3.25 ± 0.9 SDS) within the first 4 years of age, and 36 SGA children who caught up growth (0.20 ± 1.1 SDS). PCR products of all coding IGF1R exons were screened by dHPLC followed by direct sequencing of conspicuous fragments to identify small nucleotide variants. The presence of IGF1R gene copy number alterations was determined by Multiplex Ligation-dependent Probe Amplification (MLPA).
The cohort of short SGA born children revealed a heterozygous, synonymous variant c.3453C > T in one patient and a novel heterozygous 3 bp in-frame deletion (c.3234_3236delCAT) resulting in one amino acid deletion (p.Ile1078del) in another patient. The first patient had normal serum levels of IGF1. The second patient had unusually low IGF1 serum concentrations (-1.57 SD), which contrasts previously published data where IGF1 levels rarely are found below the age-adjusted mean.
gene alterations were present in 2 of 64 short SGA children. The patients did not have any dysmorphic features or developmental delay. It is remarkable that one of them had significantly decreased serum concentrations of IGF1. Growth response to GH treatment in one of the patients was favourable, while the second one discontinued the treatment, but with catch-up growth.
小于胎龄（SGA）出生的儿童是一个异质性群体，报道的遗传病因较少。在一些SGA儿童中发现了胰岛素样生长因子1受体（IGF1R）的基因改变。
研究SGA出生儿童中是否存在基因改变。
我们分析了64名SGA出生且在4岁前身高增长缓慢（平均-3.25±0.9 SDS）的儿童，以及36名实现追赶生长（0.20±1.1 SDS）的SGA儿童。通过变性高效液相色谱（dHPLC）筛选IGF1R所有编码外显子的PCR产物，随后对明显片段进行直接测序以鉴定小核苷酸变异。通过多重连接依赖探针扩增（MLPA）确定IGF1R基因拷贝数改变的存在。
身高增长缓慢的SGA出生儿童队列中，一名患者发现杂合同义变异c.3453C>T，另一名患者发现一个新的杂合3 bp框内缺失（c.3234_3236delCAT），导致一个氨基酸缺失（p.Ile1078del）。第一名患者的IGF1血清水平正常。第二名患者的IGF1血清浓度异常低（-1.57 SD），这与之前发表的数据形成对比，之前的数据显示IGF1水平很少低于年龄校正均值。
64名身高增长缓慢的SGA儿童中有2名存在基因改变。这些患者没有任何畸形特征或发育迟缓。值得注意的是，其中一名患者的IGF1血清浓度显著降低。一名患者对生长激素治疗的生长反应良好，而另一名患者停止了治疗，但实现了追赶生长。
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