Primary Ovarian Insufficiency_Premature Ovarian Failure

Gene: FLRT3

Red List (low evidence)

Insufficient evidence for FLRT3 as a monogenic cause of hypogonadotropic hypogonadism, although it is a candidate gene based on its involvement in the FGFR1 signaling pathway. Most individuals found to have variants in this gene also have variants in other genes in this signalling pathway. PMID: 23643382: three probands with Kallman syndrome identified with missense FLRT3 variants, however one also had a FGFR1 variant (the FLRT3 variant was also present in gnomAD (7 heterozygotes)) and one also had FGFR1, HS6ST1, and FGF17 variants (this individual had a homozygous missense FLRT3 variant and a heterozygous missense FLRT3 variant, both absent from gnomAD). No functional studies were performed on any of the variants. PMID: 31200363: one proband with normosmic congenital hypogonadotropic hypogonadism with a missense FLRT3 variant, however this missense variant is present in gnomAD (22 heterozygotes) and it was found along with a missense variant in POLR3A. No functional studies were performed on any of the variants.

Created: 3 Jul 2020, 3:06 a.m. | Last Modified: 3 Jul 2020, 3:06 a.m.

Panel Version: 0.3211

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271)

Publications

• 23643382
• 31200363

Red List (low evidence)

Insufficient evidence for FLRT3 as a monogenic cause of hypogonadotropic hypogonadism, although it is a candidate gene based on its involvement in the FGFR1 signaling pathway. Most individuals found to have variants in this gene also have variants in other genes in this signalling pathway.

PMID: 23643382: three probands with Kallman syndrome identified with missense FLRT3 variants, however one also had a FGFR1 variant (the FLRT3 variant was also present in gnomAD (7 heterozygotes)) and one also had FGFR1, HS6ST1, and FGF17 variants (this individual had a homozygous missense FLRT3 variant and a heterozygous missense FLRT3 variant, both absent from gnomAD). No functional studies were performed on any of the variants.

PMID: 31200363: one proband with normosmic congenital hypogonadotropic hypogonadism with a missense FLRT3 variant, however this missense variant is present in gnomAD (22 heterozygotes) and it was found along with a missense variant in POLR3A. No functional studies were performed on any of the variants.

Created: 2 Jul 2020, 11:34 p.m. | Last Modified: 2 Jul 2020, 11:34 p.m.

Panel Version: 0.31

Mode of inheritance
Unknown

Phenotypes
Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271)

Publications

• PMID: 23643382
• 31200363