title: PROKR2 mutations in autosomal recessive Kallmann syndrome.
abstract: OBJECTIVE
  To investigate the inheritance pattern of two missense PROKR2 changes within a single family.
  
  
  METHODS
  This is a descriptive study.
  
  
  METHODS
  Tertiary referral center.
  
  
  METHODS
  The proband and his brother, both with congenital hypogonadotropic hypogonadism and anosmia (Kallmann syndrome).
  
  
  METHODS
  Clinical and biochemical evaluation of Kallmann syndrome. Sequence analysis of the coding exons and exon-intron boundaries of KAL1, FGFR1, FGF8, PROK2, and PROKR2 from polymerase chain reaction (PCR)-amplified genomic DNA. Recombinant human FSH treatment of the proband.
  
  
  METHODS
  Phenotypic and genotypic features, and inhibin B response to recombinant human FSH.
  
  
  RESULTS
  The proband and his brother were homozygous for two variants in PROKR2; a novel mutation c.701G>A (p.G234D), and a polymorphism c.802C>T (p.R268C). Recombinant human FSH therapy of the proband increased serum inhibin B from <16 to 136 ng/L. The heterozygous parents were fertile and had six children.
  
  
  CONCLUSIONS
  These findings are consistent with recessive mode of inheritance. PROKR2 signaling does not directly affect Sertoli cell function.
authors.affiliation: Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Tommiska
authors.forename: Jorma
authors.initials: J
authors.lastname: Toppari
authors.forename: Kirsi
authors.initials: K
authors.lastname: Vaaralahti
authors.forename: Johanna
authors.initials: J
authors.lastname: Känsäkoski
authors.forename: Eeva-Maria
authors.initials: EM
authors.lastname: Laitinen
authors.forename: Parinya
authors.initials: P
authors.lastname: Noisa
authors.forename: Anne
authors.initials: A
authors.lastname: Kinnala
authors.forename: Harri
authors.initials: H
authors.lastname: Niinikoski
authors.forename: Taneli
authors.initials: T
authors.lastname: Raivio
mesh_terms: D000293:Adolescent; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D017436:Kallmann Syndrome / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D018000:Receptors, Peptide / Q000235:genetics* / Q000378:metabolism; D012708:Sertoli Cells / Q000502:physiology; D035781:Siblings; D015398:Signal Transduction / Q000235:genetics
chemical_list: C470838:PROKR2 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide