目的 分析特发性矮小患者中基因变异种类并量化基因变异频率,为特发性矮小病因诊断提供新思路。方法 回顾性分析2017年7月—2022年7月解放军总医院第四、第五医学中心儿科内分泌门诊208例特发性矮小患者的临床资料,对疑似遗传变异患儿进行遗传学分析,探寻潜在遗传病理机制。结果 208例特发性矮小患儿中22例患者经初步筛查存在可疑遗传变异并行遗传学分析,发现7种基因变异类型,分别为FGD1、FGFR1、ACAN、SLC26A4、CREBBP、ACTB与KAT6A基因的变异,共8例基因变异患者。特发性矮小患者群体中累计基因变异检出率约3.85%,临床疑似遗传变异患者经遗传分析确诊率约36.4%。结论 特发性矮小的发生与遗传基因变异密切相关,临床表征分析结合分子遗传学技术检测能够发现不同类型的生长板发育相关遗传变异,为明确特发性矮小的病因提供帮助。
Abstract
Objective To analyze the types and frequency of genetic variation in children with idiopathic short stature (ISS), in order to provide new ideas for the diagnosis and treatment of ISS. Methods Clinical data of 208 children with ISS in the pediatric endocrinology outpatient of the Fourth and the Fifth Medical Center of PLA General Hospital from July 2017 to July 2022 were retrospectively analyzed, and genetic analysis was performed on patients with suspicious genetic variation to explore the potential genetic pathological mechanism. Results Among 208 children with ISS, 22 children showed suspicious genetic variation through preliminary screening and genetic analysis. Seven types of genetic variation in 8 children with genetic variation were detected by whole exon sequencing and copy number variation analysis techniques, including variations in FGD1, FGFR1, ACAN, SLC26A4, CREBBP, ACTB and KAT6A. The cumulative detection rate of genetic variation in patients with idiopathic short stature was about 3.85%, and the diagnosis rate by genetic analysis was about 36.4% in patients with clinically suspected genetic variation. Conclusions The occurrence of ISS is closely related to genetic variation. Through clinical characterization analysis and molecular genetics detection, different types of genetic variation related to growth plate development can be found, which can help to clarify the etiology of ISS.
关键词
特发性矮小 /
生长板 /
遗传分析 /
基因变异
Key words
idiopathic short stature /
growth plate /
genetic analysis /
genetic variation
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参考文献
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