PROKR2 mutations in autosomal recessive Kallmann syndrome

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

Authors:
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

Abstract:

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

Design:
This is a descriptive study.

Setting:
Tertiary referral center.

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

Intervention(s):
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.

Result(s):
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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