摘要目的 探讨两个高促性腺激素闭经同时窦状卵泡数目正常家系的遗传学病因,为遗传咨询及生育指导提供依据.方法 应用PCR-Sanger测序的方法对2个高促性腺激素闭经家系促性腺激素受体基因(FSHR和LHCGR)进行检测,在找到可疑致病突变的情况下进行家系分析,并对该可疑突变进行生物信息学分析,预测其致病性.结果 家系1和家系2先证者FSHR基因分别存在尚未报道的c.419delA(p.Lys140Argfs* 16)纯合突变和c.1510C＞T(p.Pr0504Ser)纯合突变.通过家系分析及生物信息学分析,该2个突变均为致病突变的可能性大,文献回顾这两个家系患者均为卵巢抵抗综合征而非卵巢早衰.结论发现两个卵巢抵抗综合征家系的FSHR基因新突变,丰富了FSHR基因突变谱,同时为家系遗传咨询和生育指导提供了依据.

abstractsObjective To explore the genetic etiology for two Chinese families affected with hypergonadotropic amenorrhea and normal number of antral follicles.Methods Peripheral venous blood samples were collected from the families for the extraction of genomic DNA.Mutations of FSHR and LHCGR genes were screened using PCR and Sanger sequencing.Suspected pathogenic mutations were verified in other members of the families.Bioinformatics software and NCBI were used to analyze the pathogenicity of the mutations.Results Two previously unreported homozygous mutations,c.419delA and c.1510C＞T of the FSHR gene were found in the probands of family Ⅰ and Ⅱ,respectively.Pedigree and bioinformatics analysis suggested that both mutations were pathogenic.Literature review suggested that both families were affected with resistant ovary syndrome rather than premature ovarian failure.Conclusion Two novel mutations of the FSHR gene have been identified,which have enriched the spectrum of FSHR gene mutations and provided a basis for genetic counseling and direction for reproduction.