Pituitary hormone deficiency
Gene: SIX3
Two children with combined pituitary hormone deficiency and thin pituitary stalk from a single family were found to be doubly heterozygous for missense variants in SIX3 and POU1F1. A third affected sibling was not available for testing. Two other siblings without pituitary hormone deficiency were not doubly heterozygous for the SIX3 and POU1F1 variants. The SIX3 variant has 46 heterozygotes in gnomAD; the POU1F1 variant is novel.
Functional testing showed the SIX3 variant has weaker activation activity than wild type. Six3 and Pou1f1 doubly heterozygous mice were shown to have abnormal pituitary and palate morphology and reduced viability.Created: 1 Sep 2022, 6:54 a.m. | Last Modified: 1 Sep 2022, 6:54 a.m.
Panel Version: 0.26
Mode of inheritance
Other
Phenotypes
Non-acquired combined pituitary hormone deficiency MONDO:0018762
Publications
Variants in this GENE are reported as part of current diagnostic practice
Gene: six3 has been classified as Red List (Low Evidence).
Phenotypes for gene: SIX3 were changed from Holoprosencephaly 2 (157170); Non-acquired combined pituitary hormone deficiency MONDO:0018762 to Holoprosencephaly 2 (157170); Non-acquired combined pituitary hormone deficiency MONDO:0018762
Phenotypes for gene: SIX3 were changed from Holoprosencephaly 2 (157170) to Holoprosencephaly 2 (157170); Non-acquired combined pituitary hormone deficiency MONDO:0018762
Publications for gene: SIX3 were set to
gene: SIX3 was added gene: SIX3 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red Mode of inheritance for gene: SIX3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SIX3 were set to Holoprosencephaly 2 (157170)