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Pituitary hormone deficiency v1.2 JAG1 chirag patel gene: JAG1 was added
gene: JAG1 was added to Pituitary hormone deficiency. Sources: Literature
Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JAG1 were set to 36729644
Phenotypes for gene: JAG1 were set to Hypogonadotropic hypogonadism, MONDO:0015770, JAG1-related
Review for gene: JAG1 was set to AMBER
Added comment: 9 unrelated individuals with heterozygous missense JAG1 variants presenting with congenital hypogonadotropic hypogonadism/Kallmann syndrome (GnRH deficiency) and no features of Alagille syndrome. There was no segregation data. Some individuals (6/9) had variants in other HH genes. The ultra‑rare variants (p.R117G, p.F206Y, p.T931I, p.F509L) reduce JAG1 protein levels or cause ER retention in HEK293T cells, and jag1b knock‑down in zebrafish disrupts GnRH neuron migration.
Sources: Literature
Pituitary hormone deficiency v1.0 BRAF Gene migrated from ENSG00000157764 to ENSG00000157764 (gene set migration)
Pituitary hormone deficiency v0.152 BRAF chirag patel Marked gene: BRAF as ready
Pituitary hormone deficiency v0.152 BRAF chirag patel Gene: braf has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.50 BRAF chirag patel Classified gene: BRAF as Green List (high evidence)
Pituitary hormone deficiency v0.50 BRAF chirag patel Gene: braf has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.49 BRAF chirag patel gene: BRAF was added
gene: BRAF was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp
Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRAF were set to 33795686
Phenotypes for gene: BRAF were set to Cardiofaciocutaneous syndrome, MONDO:0015280
Review for gene: BRAF was set to GREEN
Added comment: 5 unrelated patients with Cardio-Facio-Cutaneous (CFC) syndrome and 4 different missense variants in BRAF. They all had features of Septo-Optic Dysplasia with hypopituitarism. Functional studies using HEK293T cells showed that the BRAF genetic variants are pathogenic and result in activation of the ERK/MAPK pathway. Mice expressing one of the variants found BRAF p.Q257R showed abnormalities in terminal differentiation of hormone-producing cells causing hypopituitarism.
Sources: Genomics England PanelApp