PROKR2 mutations in autosomal recessive Kallmann syndrome

Report describes two brothers with two homozygous PROKR2 missense changes and Kallmann syndrome, and their healthy heterozygous carrier parents.

Johanna Tommiska, Ph.D., Jorma Toppari, M.D., Ph.D., Kirsi Vaaralahti, M.Sc., Johanna Känsäkoski, B.Sc., Eeva-Maria Laitinen, M.D., Parinya Noisa, Ph.D., Anne Kinnala, M.D., Harri Niinikoski, M.D., Taneli Raivio, M.D., Ph.D.

Volume 99, Issue 3, Pages 815-818, 1 March 2013


To investigate the inheritance pattern of two missense PROKR2 changes within a single family.

This is a descriptive study.

Tertiary referral center.

The proband and his brother, both with congenital hypogonadotropic hypogonadism and anosmia (Kallmann syndrome).

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.

Main Outcome Measure(s):
Phenotypic and genotypic features, and inhibin B response to recombinant human FSH.

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. Conclusion(s):
These findings are consistent with recessive mode of inheritance. PROKR2 signaling does not directly affect Sertoli cell function.

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