Kallmann syndrome with a Tyr113His PROKR2 mutation.

RATIONAL: Kallmann syndrome (KS) is a genetic gonadotropin-releasing hormone deficiency associated with hyposmia or anosmia and characterized by various modes of inheritance.

PATIENT CONCERNS: A 16-year-old male did not reach puberty and was associated with hypogonadotropic hypogonadism and anosmia. His magnetic resonance imaging of brain revealed the absence of the olfactory bulb.

DIAGNOSIS: His karyotype was 46 XY. Sanger sequencing of the KAL1 gene revealed no mutations. Diagnostic exome sequencing identified a prokineticin-receptor 2 (PROKR2) gene variant, c.337T > C (p.Tyr113His), previously reported to be a pathogenic mutation; we confirmed the presence of the mutation via Sanger sequencing of the coding exons of PROKR2. His apparently unaffected mother and sister, but not his father, were heterozygous for the PROKR2 Tyr113His mutation.

LESSONS: This work advances our understanding of the role played by PROKR signaling and the mode of inheritance of the gene in patients with KS.