Elsevier

Fertility and Sterility

Volume 96, Issue 2, August 2011, Pages e125-e130
Fertility and Sterility

Original article
Case report
Inherited mutation of the luteinizing hormone/choriogonadotropin receptor (LHCGR) in empty follicle syndrome

https://doi.org/10.1016/j.fertnstert.2011.05.057Get rights and content
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Objective

To test by genomic analysis whether empty follicle syndrome (EFS) in a family with two affected sisters has a genetic basis.

Design

Whole-exome sequencing in the context of clinical genetics.

Setting

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.

Key Words

Empty follicle syndrome
luteinizing hormone/choriogonadotropin receptor
infertility
next-generation sequencing

Cited by (0)

K.O.Y. has nothing to disclose. T.W. has nothing to disclose. A.U. has nothing to disclose. M.S. has nothing to disclose. D.D. has nothing to disclose. G.O. has nothing to disclose. M-C.K. has nothing to disclose. M.T. has nothing to disclose.

Supported in part by grants R01DC009645 and R01DC005641 from the National Institute of Deafness and other Communication Disorders of the National Institutes of Health with a supplement from the American Recovery and Reinvestment Act.