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目的研究先天性甲状腺功能减退症(甲减)患者的TSH受体(TSHR)基因突变与家系遗传规律。方法用TKM法提取18例先天性甲减患者、35名正常对照者外周血白细胞DNA,PCR-SSCP分析TSHR基因第1、4、6、10号外显子,突变经正反向测序证实。分析先证者家系成员TSHR基因与甲状腺功能情况。结果发现1例先天性甲减患儿在TSHR基因第10号外显子有2个位点纯合子突变:450位密码子CGC置换为CAC,Arg450→His(R450H);727位密码子GAC置换为GAG,Asp727→Glu(D727E)。调查家系成员10人,6人为R450H/D727E复合杂合子,以女性携带为主,先证者的父母均为复合杂合子,杂合子中5人血清sTSH轻度升高,为亚临床甲状腺功能减退症(亚临床甲减)。结论R450H/D727E纯合子突变导致先天性甲减,R450H/D727E杂合子突变可发生亚临床甲减。
Objective To study the TSHR gene mutation and pedigree inheritance in patients with congenital hypothyroidism (hypothyroidism). Methods 18 cases of congenital hypothyroidism and 35 normal control were collected by TKM method. The exon 1, 4, 6 and 10 of TSHR gene were analyzed by PCR-SSCP. The mutations were confirmed by reverse-sequencing. Analysis of proband family members TSHR gene and thyroid function. One congenital hypothyroidism was found in two sites of TSHR gene exon 10 homozygous mutations: 450 codons CGC replaced CAC, Arg450 → His (R450H); 727 codons GAC replaced by GAG, Asp727 → Glu (D727E). The survey family members 10, 6 were R450H / D727E compound heterozygous, mainly female carriers, proband parents are complex heterozygotes, heterozygous sTSH serum 5 were slightly elevated for subclinical hypothyroidism Symptoms (subclinical hypothyroidism). Conclusion The homozygous mutation of R450H / D727E results in congenital hypothyroidism, and subclinical hypothyroidism may occur in R450H / D727E heterozygous mutation.