先天性甲状腺功能减退症患儿DUOX2基因突变的研究

目的 研究先天性甲状腺功能减退症(congenital hypothyroidism, CH)患儿DUOX2 基因突变类型和特点,并初步探讨基因型- 表现型的关系,为CH 患儿的基因诊断和基因治疗提供理论依据.方法 从10例CH 伴甲状腺肿大患儿外周血白细胞中提取基因组DNA,采用PCR 扩增和直接测序的方法对DUOX2 全部外显子进行基因突变检测.结果 在1 例患儿中发现DUOX2 基因第28 外显子cDNA 的3632 位点发生了G>A 的突变(c.G3632A),导致第1 211 密码子的精氨酸变为组氨酸(p.R1211H).在3 例患儿中发现DUOX2 基因第17 外显子cDNA 的2 033 位点发生了T>C 的突变(c.T2033C),导致第678 密码子的组氨酸变为精氨酸(p.H678R).此两种突变均为杂合型的错义突变.结论 CH 患儿存在DUOX2 基因杂合突变,该杂合突变可能引起蛋白质功能的改变从而导致CH;基因型与表现型的关系尚不明确,需要进一步的研究.

DUOX2 mutations in children with congenital hypothyroidism

Objective To study the features of DUOX2 mutations and genotype-phenotype relationship in children with congenital hypothyroidism (CH), in order to provide evidence for gene diagnosis and gene treatment of CH. Methods Blood samples were collected from 10 CH children with thyromegaly. Genomic DNA was extracted from peripheral blood leukocytes. All exons of DUOX2 gene were analyzed using PCR and direct sequencing. Results G3632A mutation in the exon 28 of DUOX2 that may result in arginine to histidine substitution at codon 1211 was found in one patient. T2033C mutation in the exon 17 of DUOX2 that may result in histidine to arginine substitution at codon 678 was found in three patients. They were all heterozygous mutations. Conclusions Heterozygous mutations in DUOX2 may affect protein function and cause CH. The relationship between DUOX2 genotypes and clinical phenotypes is unclear and needs further studies.