Pituitary hormone deficiency

Gene: SIX3

Red List (low evidence)

Comment on list classification: There is not enough evidence for this gene to be rated GREEN at the next major review.

Created: 22 Sep 2022, 12:40 p.m. | Last Modified: 22 Sep 2022, 12:40 p.m.

Panel Version: 2.96

Associated with Holoprosencephaly 2 (OMIM:157170) in OMIM and as definitive Gen2Phen gene for this phenotype. PMID: 35951005 reports a familiy with children with combined pituitary hormone deficiency, who are heterozygous for variants in SIX3 & POU1F1. Heterozygous Six3 variant mouse models reported in the same paper have pituitary gland dysmorphology and incompletely ossified palate.

Created: 22 Sep 2022, 12:39 p.m. | Last Modified: 22 Sep 2022, 12:39 p.m.

Panel Version: 2.95

Review on behalf of Professor Mehul Dattani, UCL GOS Institute of Child Health/Great Ormond Street Hospital for Children. AD - ?COMBINATION WITH OTHER PITUITARY GENES. Bando H, Brinkmeier ML, Castinetti F, Fang Q, Lee MS, Saveanu A, Albarel F, Dupuis C, Brue T, Camper SA.Hum Mol Genet. 2022 Aug 11:ddac192. doi: 10.1093/hmg/ddac192. Online ahead of print.PMID:35951005

Created: 14 Sep 2022, 4:44 p.m. | Last Modified: 14 Sep 2022, 4:44 p.m.

Panel Version: 2.15

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
HYPOPITUITARISM

Publications

• 35951005

Comment on list classification: Demoted from amber to red. SIX3 is confirmed to be associated with Holoprosencephaly in OMIM and Gene2Phenotype and is a green gene on the Holoprosencephaly gene panel (Version 1.6). However, there is no evidence that patients with Holoprosencephaly with variants in the SIX3 gene has pituitary hormone deficiency.

Created: 14 Dec 2018, 2:26 p.m.