CAJ | 학술논문

目的分析Laron综合征临床特点及基因突变,阐明矮小患者诊断思路.方法分析1例极度矮小患儿的临床特征并行辅助检查,评定生长激素-胰岛素样生长因子-1(GH-IGF-1)轴功能并对其家系成员进行调查；提取患儿及部分家系成员外周血基因组DNA,PCR扩增GHR、IGFALS、STAT5b及GHI基因的外显子及与内含子拼接区进行测序分析.结果患儿表现为匀称性身材矮小(身高-8.2 SDS)及特殊面容,无其他先天性畸形及异常.实验室检查提示非生长激素缺乏,生长激素基础值21 μg/L,峰值57.9 μg/L,胰岛素样生长因子＜25 μg/L,胰岛素样生长因子结合蛋白-3＜ 50μg/L,且对胰岛素样生长因子生成试验无反应.家族成员中无类似疾病患者.GHR基因检测显示患儿存在c.Ivs6+ 1G＞A纯合突变,其父母均为杂合突变.其他候选基因测序分析未发现异常.结论通过临床表型及生化特征分析,结合基因检测,确诊患儿为Laron综合征,GHR基因突变是其致病原因.
목적 분석Laron종합정림상특점급기인돌변,천명왜소환자진단사로.방법 분석1례겁도왜소환인적림상특정병행보조검사,평정생장격소-이도소양생장인자-1(GH-IGF-1)축공능병대기가계성원진행조사；제취환인급부분가계성원외주혈기인조DNA,PCR확증GHR、IGFALS、STAT5b급GHI기인적외현자급여내함자병접구진행측서분석.결과 환인표현위균칭성신재왜소(신고-8.2 SDS)급특수면용,무기타선천성기형급이상.실험실검사제시비생장격소결핍,생장격소기출치21 μg/L,봉치57.9 μg/L,이도소양생장인자＜25 μg/L,이도소양생장인자결합단백-3＜ 50μg/L,차대이도소양생장인자생성시험무반응.가족성원중무유사질병환자.GHR기인검측현시환인존재c.Ivs6+ 1G＞A순합돌변,기부모균위잡합돌변.기타후선기인측서분석미발현이상.결론 통과림상표형급생화특정분석,결합기인검측,학진환인위Laron종합정,GHR기인돌변시기치병원인.
Objective To analyze clinical manifestations and gene mutations in a child with severe short stature,explore its molecular mechanism and further clarify the diagnostic procedure for short stature.Method We observed clinical characteristics of a patient with short stature and did diagnostic examinations,assessed the function of GH-IGF-1 axis,and surveyed its family members.Genomic DNA was extracted from peripheral blood,GHR,IGFALS,STAT5b and GH1 gene were amplified by PCR for sequencing,including exons and splicing areas.Result The patient presented symmetrical short stature (height-8.2 SDS) and facial features,and other congenital abnormalities.It displayed non-growth hormone deficiency.The baseline value of GH was 21 μg/L,and the peak was 57.9 μg/L The value of IGF-1 was less than 25 μg/L,and the IGFBP-3 less than 50 μg/L And IGF-1 generation test showed no response.There was no similar patients in the family members.Sequencing of GHR in the patient revealed a homozygous point mutation (c.Ivs6 + 1G ＞ A),and her father and mother had the same heterozygous mutation.The same mutation was not identified for her sister.No other candidate gene was found.Conclusion As the result of combined clinical characteristics and lab examinations,as well as gene detection,the case was diagnosed with Laron syndrome and GHR gene mutation is the molecular mechanism.We should explicit the etiological diagnosis for short stature,and avoid missed diagnosis and misdiagnosis.