西南地区人群PHOX2B基因GCN重复变异的调查以及2例先天性中枢性低通气综合征患儿的诊断  

Study of GCN repeats of PHOX2B gene among individuals from southwest China and diagnosis of two patients with Congenital central hypoventilation syndrome

作　　者：秦胜芳[1] 叶梦玲[1] 尹雁 王锦 汪雪雁[1] 张卓 陈希敏 严梦珈 何玉霞 易丹英 邓琴 Qin Shengfang;Ye Mengling;Yin Yan;Wang Jin;Wang Xueyan;Zhang Zhuo;Chen Ximin;Yan Mengjia;He Yuxia;Yi Danying;Deng Qin(Department of Medical Genetics and Prenatal Diagnosis,Sichuan Provincial Maternity and Child Health Care Hospital,Chengdu,Sichuan 610045,China)

机构地区：[1]四川省妇幼保健院医学遗传与产前诊断科,成都610045

出　　处：《中华医学遗传学杂志》2024年第1期32-37,共6页Chinese Journal of Medical Genetics

摘　　要：目的调查西南地区健康人群PHOX2B基因第3外显子编码丙氨酸的GCN(GCA、GCT、GCC、GCG)三碱基重复数的分布,并对2例先天性中枢性低通气综合征(CCHS)患儿的GCN重复数进行分析。方法分别采用毛细管电泳分析、Sanger测序、克隆测序分析518例健康个体和2例CCHS患儿及其父母PHOX2B基因的GCN重复数和碱基序列。结果对518例健康个体的1036个等位基因进行分析,共发现5种等位基因,其中以(GCN)20频率最高,达94.79%;共发现5种基因型,其中(GCN)20/(GCN)20纯合子占89.58%。(GCN)20纯合基因型由4种不同的GCN重复碱基序列组成。PHOX2B基因GCN重复的基因型在调查人群中达到了遗传平衡。两例CCHS患儿的基因型分别为(GCN)20/(GCN)25和(GCN)20/(GCN)30。结论调查正常人群中PHOX2B的GCN重复数分布和基因型数据具有重要的意义。518例健康个体的GCN重复数均在20以下。准确检出PHOX2B基因的重复扩增突变将有助于CCHS的早期诊断和治疗。Objective To study the trinucleotide repeats of GCN(GCA,GCT,GCC,GCG)encoding Alanine in exon 3 of the PHOX2B gene among healthy individuals from southwest China and two patients with Congenital central hypoventilation syndrome(CCHS).Methods The number and sequence of the GCN repeats of the PHOX2B gene were analyzed by capillary electrophoresis,Sanger sequencing and cloning sequencing of 518 healthy individuals and two newborns with CCHS,respectively.Results Among the 1036 alleles of the 518 healthy individuals,five alleles were identified,including(GCN)7,(GCN)13,(GCN)14,(GCN)15 and(GCN)20.The frequency of the(GCN)20 allele was the highest(94.79%).And five genotypes were identified,which included(GCN)7/(GCN)20,(GCN)13/(GCN)20,(GCN)14/(GCN)20,(GCN)15/(GCN)20,(GCN)20/(GCN)20.The homozygous genotypes were all(GCN)20/(GCN)20,and the carrier rate was 89.58%.Four GCN sequences of the(GCN)20 homozygous genotypes were identified among the 464 healthy individuals.The GCN repeat numbers in the exon 3 of the PHOX2B gene showed no significant difference between the expected and observed values,and had fulfilled the,Hardy-Weinberg equilibrium.The genotypes of the two CCHS patients were(GCN)20/(GCN)25 and(GCN)20/(GCN)30,respectively.Conclusion It is important to determine the GCN repeats and genotypic data of the exon 3 of the PHOX2B gene among the healthy individuals.The number of GCN repeats in 518 healthy individuals was all below 20.The selection of appropriate methods can accurately detect the polyalanine repeat mutations(PARMs)of the PHOX2B gene,which is conducive to the early diagnosis,intervention and treatment of CCHS.

关 键 词：PHOX2B基因 GCN重复 基因测序 毛细管电泳 先天性中枢性低通气综合征 

分 类 号：R725.9[医药卫生—儿科]