Department of Human Genetics and Institute for Human Genomics, University of Miami School of Medicine, Miami, Florida, USA.
Fertil Steril. 2011 Aug;96(2):e125-30. doi: 10.1016/j.fertnstert.2011.05.057. Epub 2011 Jun 17.
To test by genomic analysis whether empty follicle syndrome (EFS) in a family with two affected sisters has a genetic basis.
Whole-exome sequencing in the context of clinical genetics.
University hospital.
PATIENT(S): Two women (36 and 32 years old at the time of the study) with EFS.
INTERVENTION(S): Genetic counseling based on autosomal recessive inheritance.
MAIN OUTCOME MEASURE(S): Discovery of a mutation in the LH/choriogonadotropin receptor (LHCGR) as the cause of EFS.
RESULT(S): A novel missense mutation in LHCGR, p.N400S, was homozygous in sisters with EFS and/or infertility, but not in their unaffected siblings or parents. The mutation was not present in 500 ancestry-matched control subjects. Asparagine at residue 400 is highly conserved and its substitution by serine predicted to alter critical interactions that stabilize LHCGR.
CONCLUSION(S): We describe a genetic basis for EFS and provide strong evidence for the existence of genuine EFS in some patients. A mutation impairing the function of LHCGR explains the lack of response of these patients to repeated administration of β-hCG.
通过基因组分析检测一个有两名患病姐妹的家族中的空卵泡综合征（EFS）是否具有遗传基础。
临床遗传学背景下的全外显子测序。
大学医院。
两名女性（研究时分别为 36 岁和 32 岁）患有 EFS。
基于常染色体隐性遗传的遗传咨询。
发现 LH/促性腺激素受体（LHCGR）突变是 EFS 的病因。
EFS 和/或不孕的姐妹均为 LHCGR 中的新型错义突变纯合子，p.N400S，而未受影响的兄弟姐妹或父母则没有。该突变在 500 名与对照组无亲缘关系的对照个体中不存在。第 400 位的天冬酰胺高度保守，其被丝氨酸取代预计会改变稳定 LHCGR 的关键相互作用。
我们描述了 EFS 的遗传基础，并为一些患者中存在真正的 EFS 提供了有力证据。该突变损害了 LHCGR 的功能，解释了这些患者对重复给予β-hCG 无反应的原因。
