title: Inherited mutation of the luteinizing hormone/choriogonadotropin receptor (LHCGR) in empty follicle syndrome.
abstract: OBJECTIVE
  To test by genomic analysis whether empty follicle syndrome (EFS) in a family with two affected sisters has a genetic basis.
  
  
  METHODS
  Whole-exome sequencing in the context of clinical genetics.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Two women (36 and 32 years old at the time of the study) with EFS.
  
  
  METHODS
  Genetic counseling based on autosomal recessive inheritance.
  
  
  METHODS
  Discovery of a mutation in the LH/choriogonadotropin receptor (LHCGR) as the cause of EFS.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Human Genetics and Institute for Human Genomics, University of Miami School of Medicine, Miami, Florida, USA.
authors.forename: Kemal O
authors.initials: KO
authors.lastname: Yariz
authors.forename: Tom
authors.initials: T
authors.lastname: Walsh
authors.forename: Asli
authors.initials: A
authors.lastname: Uzak
authors.forename: Michail
authors.initials: M
authors.lastname: Spiliopoulos
authors.forename: Duygu
authors.initials: D
authors.lastname: Duman
authors.forename: Gogsen
authors.initials: G
authors.lastname: Onalan
authors.forename: Mary-Claire
authors.initials: MC
authors.lastname: King
authors.forename: Mustafa
authors.initials: M
authors.lastname: Tekin
mesh_terms: D000328:Adult; D006063:Chorionic Gonadotropin / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005298:Fertility / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006720:Homozygote; D006801:Humans; D007247:Infertility, Female / Q000235:genetics* / Q000503:physiopathology; D008958:Models, Molecular; D020125:Mutation, Missense; D010049:Ovarian Diseases / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D011487:Protein Conformation; D011974:Receptors, LH / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013577:Syndrome
chemical_list: D006063:Chorionic Gonadotropin; D011974:Receptors, LH