Pituitary hormone deficiency
Gene: BRAF
The rating of this gene has been updated to GREEN and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.Created: 31 Jan 2023, 3:01 p.m. | Last Modified: 31 Jan 2023, 3:01 p.m.
Panel Version: 2.106
Comment on list classification: Promoting from red to amber, but with a green recommendation following GMS review. 5 cases reported with functional data implicating pituitary hormone deficiencies.Created: 16 Sep 2022, 4:37 p.m. | Last Modified: 16 Sep 2022, 4:37 p.m.
Panel Version: 2.31
Comment on mode of pathogenicity: All missense, activating variantsCreated: 16 Sep 2022, 4:36 p.m. | Last Modified: 16 Sep 2022, 4:36 p.m.
Panel Version: 2.28
PMID: 33795686 - Gualtieri et al 2021 - report 5 unrelated patients with 4 different missense variants in BRAF. WES did not find any other likely causative variants. They all had Cardio-Facio-Cutaneous (CFC) syndrome and were identified to have features of Septo-Optic Dysplasia (SOD). 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.Created: 16 Sep 2022, 4:36 p.m. | Last Modified: 16 Sep 2022, 4:36 p.m.
Panel Version: 2.26
Review on behalf of Professor Mehul Dattani, UCL GOS Institute of Child Health/Great Ormond Street Hospital for Children. Gualtieri A, Kyprianou N, Gregory LC, Vignola ML, Nicholson JG, Tan R, Inoue SI, Scagliotti V, Casado P, Blackburn J, Abollo-Jimenez F, Marinelli E, Besser REJ, Hgler W, Karen Temple I, Davies JH, Gagunashvili A, Robinson ICAF, Camper SA, Davis SW, Cutillas PR, Gevers EF, Aoki Y,Dattani MT, Gaston-Massuet C.Nat Commun. 2021 Apr 1;12(1):2028. doi: 10.1038/s41467-021-21712-4.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
Cardiofaciocutaneous syndrome, OMIM:115150; cardiofaciocutaneous syndrome, MONDO:0015280
Publications
Tag Q3_22_rating was removed from gene: BRAF. Tag Q3_22_NHS_review was removed from gene: BRAF.
Source Expert Review Green was added to BRAF. Source NHS GMS was added to BRAF. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: braf has been classified as Amber List (Moderate Evidence).
Tag Q3_21_NHS_review was removed from gene: BRAF. Tag Q3_22_NHS_review tag was added to gene: BRAF.
Tag Q3_21_NHS_review tag was added to gene: BRAF. Tag Q3_22_rating tag was added to gene: BRAF.
Gene: braf has been classified as Red List (Low Evidence).
Phenotypes for gene: BRAF were changed from to Cardiofaciocutaneous syndrome, OMIM:115150; cardiofaciocutaneous syndrome, MONDO:0015280
Publications for gene: BRAF were set to
Mode of pathogenicity for gene: BRAF was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mode of inheritance for gene: BRAF was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
gene: BRAF was added gene: BRAF was added to Pituitary hormone deficiency. Sources: Expert review Mode of inheritance for gene: BRAF was set to