Primary Ovarian Insufficiency_Premature Ovarian Failure

Gene: FGF8

Green List (high evidence)

Loss of function variants in 8 unrelated probands with hypogonadotropic hypogonadism with or without anosmia (including Kallman syndrome). Supportive mouse model.

PMID: 20463092: two unrelated families with nonsense loss of function mutations and phenotypes including Kallman syndrome, normosmic isolated hypogonadotropic hypogonadism, delayed puberty. One family showed segregation in four affected siblings.

PMID: 18596921: six unrelated probands with missense mutations, two with FGFR1 mutations, and phenotypes including Kallman syndrome, normosmic isolated hypogonadotropic hypogonadism, absent puberty. Segregation showed some variability in phenotypes. Structural and biochemical analysis of the mutations demonstrate reduced protein function. Supportive heterozygous mouse model showing reduced number of forebrain GnRH neurons while homozygous model showed complete absence of GnRH neurons in hypothalamus and generally die within 1 day of birth.

Created: 2 Jul 2020, 2:20 a.m. | Last Modified: 2 Jul 2020, 2:20 a.m.

Panel Version: 0.18

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hypogonadotropic hypogonadism 6 with or without anosmia (612702)

Publications

• PMID: 20463092,18596921