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.
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.
Authors: Ivan A Adzhubei; Steffen Schmidt; Leonid Peshkin; Vasily E Ramensky; Anna Gerasimova; Peer Bork; Alexey S Kondrashov; Shamil R Sunyaev Journal: Nat Methods Date: 2010-04 Impact factor: 28.547
Authors: Matthew S Bramble; Ellen H Goldstein; Allen Lipson; Tuck Ngun; Ascia Eskin; Jason E Gosschalk; Lara Roach; Neerja Vashist; Hayk Barseghyan; Eric Lee; Valerie A Arboleda; Daniel Vaiman; Zafer Yuksel; Marc Fellous; Eric Vilain Journal: Hum Reprod Date: 2016-02-23 Impact factor: 6.918