中国汉族家族性激素耐药型肾病综合征家系MYO1E基因突变分析

Mutational analysis of MYO1E in Chinese children with familial steroid-resistant nephrotic syndrome

目的MY01E基因突变可导致常染色体隐性遗传型激素耐药型肾病综合征（SRNS），该研究旨在分析中国汉族家族性SRNS家系MY01E基因突变及其特点。方法2005～2010年期间共收集到4个中国汉族家族性SRNS家系，共9例肾脏病患者，选取其中4例先证者为研究对象，对照人群为59例尿检正常的健康志愿者。取所有研究对象外周静脉血3mL，提取基因组DNA；PCR扩增MY01E基因全部28个外显子及其周围的部分内含子序列；应用DNA直接测序法进行MY01E基因突变分析。结果在4个中国汉族家族性SRNS家系的先证者中共检出25个MY01E基因变异；根据对美国国立生物技术信息中心（NCBI）的单核苷酸多态性（SNP）数据库的检索，其中1个MY01E基因杂合变异（IVS21-85G〉A）首次在该研究的1个先证者中被检出，且该变异在59例正常对照人群中未检出，表明它是MY01E基因突变；另24个变异在NCBI的SNP数据库中已公布，均为MY01E基因多态性。生物信息学分析提示IVS21．85G〉A突变不导致MY01E基因剪切位点改变，为非致病性突变。结论MY01E基因突变不是该研究中国汉族SRNS家系的主要致病原因。

Objective Steroid-resistant nephrotic syndrome （SRNS） with MYO1E mutations has been identified as autosomal recessive focal segmental glomerulosclerosis （FSGS）. To date, only two homozygous mutations in the MYO1E gene were reported in three families with FSGS. This study aimed to examine mutations in the MYO1E gene in children with familial SRNS in the Hart Chinese ethnic group. Methods Between 2005 and 2010, peripheral blood samples were collected from the probands, their siblings and parents of four families with autosomal recessive SRNS in the Han Chinese ethnic group. Four probands were studied from nine patients. The mutational analysis of MYO1E was performed by polymerase chain reaction and direct DNA sequencing. Fifty-nine healthy volunteers with normal urine analysis were included as controls. Results Twenty-five MYO1E variants ha the prohands from 4 families with SRNS were identified in this study. Among them, 24 variants were found in NCBI dbSNP. One heterozygous mutation IVS21- 85G〉A was found in the prohand from Family D, whereas it was absent in 59 normal Chinese controls. No splice site change caused by IVS21-85G〉A was reported by analysis with NetGene2. Conclusions MYO1E mutations are not a major cause of Chinese familial SRNS in this study.