Differences of Sex Development

Gene: PROK2

Comment when marking as ready: Evidence supporting association between bi-allelic variants causing IHH is stronger than for mono-allelic disease.

Created: 13 Jul 2020, 8:45 a.m. | Last Modified: 13 Jul 2020, 8:45 a.m.

Panel Version: 0.66

Green List (high evidence)

>5 variants reported in heterozygous and homozygous state in patients with Kallman syndrome and normosmic idiopathic hypogonadotropic hypogonadism (nIHH). Sufficient evidence supporting gene disease association

PMID: 18559922: Reported 3 heterozygous and 1 homomozygous variant in probands with nIHH and KS, as well as a proband with variants in PROK2 and PROKR2 (digenic). 1 of the het variant (R73C) present in gnomad, 20 hets.

PMID: 17054399: Additional 4 het KS patients reported including R73C

PMID: 17959774: Two brothers with KS and their sister with nIHH reported with homozygous frameshift variant. Het carrier brother was not affected.

PMID: 18285834: 2 homozygous variants reported in 2 patients.

Green in Hypogonadotropic hypogonadism (GEL)

Created: 13 Jul 2020, 5:19 a.m. | Last Modified: 13 Jul 2020, 5:19 a.m.

Panel Version: 0.50

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Hypogonadotropic hypogonadism 4 with or without anosmia (MIM#610628)

Publications

• 18559922
• 17054399
• 17959774
• 18285834