Congenital hypothyroidism
Gene: FOXE1EnsemblGeneIds (GRCh38): ENSG00000178919
EnsemblGeneIds (GRCh37): ENSG00000178919
OMIM: 602617, Gene2Phenotype
FOXE1 is in 7 panels
2 reviews
Rebecca Foulger (Genomics England curator)
Comment when marking as ready: Rated Green by reviewer plus >3 cases supporting gene:disease association. Plus mouse model.Created: 13 Feb 2017, 12:06 p.m.
Convincing mouse model (PMID:9697704) for FOXE1 role in hypothyroidism.Created: 13 Feb 2017, 12:05 p.m.
Comment on list classification: Updated rating from Amber to Green. 1 Green review plus >3 cases (3 in OMIM plus at least PMID:24219130 in additional literature) of FOXE1 (also called TTF-2) mutations causing Bamforth-Lazarus syndrome (MIM:241850). Bamforth-Lazarus syndrome is characterized chiefly by congenital hypothyroidism (CH) due to thyroid dysgenesis (usually agenesis). Confirmed DD-G2P gene for MIM:241850.Created: 13 Feb 2017, 12:05 p.m.
Comment on mode of pathogenicity: PMID: 24219130 (Carre et al., 2014) report a new homozygous FOXE1 missense mutation (c.217C>A, p.R73S) in an Egyptian boy with Bamforth–Lazarus syndrome. In contrast to previously reported mutations, this mutation results in increased transcriptional activity of the mutant protein on the TG and TPO promoters. Thus, two different molecular mechanisms, gain and loss of function, are associated with the same phenotype (Bamforth–Lazarus syndrome).Created: 13 Feb 2017, 12:02 p.m.
Comment on mode of inheritance: Biallelic mode of inheritance confirmed by OMIM and G2P.Created: 13 Feb 2017, 11:45 a.m.
Details
- Mode of Inheritance
- BIALLELIC, autosomal or pseudoautosomal
- Sources
-
- Expert Review Green
- Eligibility statement prior genetic testing
- UKGTN
- Emory Genetics Laboratory
- Phenotypes
-
- congenital hypothyroidism
- Bamforth Lazarus syndrome, 241850 (hypothyroidism)
- Hypothyroidism, Thyroidal Or Athyroidal, With Spiky Hair And Cleft Palate, 241850
- thyroid agenesis
- cleft palate
- spiky hair
- choanal atresia
- OMIM
- 602617
- Clinvar variants
- Variants in FOXE1
- Penetrance
- Complete
- Publications
- Mode of Pathogenicity
- Other - please provide details in the comments
- Panels with this gene
History Filter Activity
panel promoted to version 1
Rebecca Foulger (Genomics England curator)22 February 2017: Promoted to Version 1. Reviews were assessed, and panel was revised according to expert review and additional curation. After discussion with the reviewer and in-house clinicians, it was agreed to include the genes for 'combined pituitary hormone deficiency' (CPHD) on the panel, since patients can present with central hypothyroidism (CH). In these cases, CH does not occur in isolation, but is one of the evolving pituitary hormone deficiencies.
Gene classified by Genomics England curator
Rebecca Foulger (Genomics England curator)This gene has been classified as Green List (High Evidence).
Set mode of pathogenicity
Rebecca Foulger (Genomics England curator)Mode of pathogenicity for FOXE1 was changed to Other - please provide details in the comments
Set publications
Rebecca Foulger (Genomics England curator)Publications for FOXE1 were set to 9697705; 20484477; 9697704 (mouse model); 24219130 (gain-of-function mutation)
Set publications
Rebecca Foulger (Genomics England curator)Publications for FOXE1 were set to 9697705; 20484477; 9697704 (mouse model); 24219130
Set Phenotypes
Rebecca Foulger (Genomics England curator)Phenotypes for FOXE1 were set to congenital hypothyroidism; Bamforth Lazarus syndrome, 241850 (hypothyroidism); Hypothyroidism, Thyroidal Or Athyroidal, With Spiky Hair And Cleft Palate, 241850; thyroid agenesis; cleft palate; spiky hair; choanal atresia
Set Phenotypes
Rebecca Foulger (Genomics England curator)Phenotypes for FOXE1 were set to congenital hypothyroidism; Bamforth Lazarus syndrome, 241850 (hyoothyroidism); Hypothyroidism, Thyroidal Or Athyroidal, With Spiky Hair And Cleft Palate, 241850; thyroid agenesis; cleft palate; spiky hair; choanal atresia
Gene classified by Genomics England curator
Rebecca Foulger (Genomics England curator)This gene has been classified as Green List (High Evidence).
Set Phenotypes
Rebecca Foulger (Genomics England curator)Phenotypes for FOXE1 were set to congenital hypothyroidism; Bamforth Lazarus syndrome; Hypothyroidism, Thyroidal Or Athyroidal, With Spiky Hair And Cleft Palate, 241850; thyroid agenesis; cleft palate; spiky hair; choanal atresia
Set publications
Rebecca Foulger (Genomics England curator)Publications for FOXE1 were set to 9697705; 20484477; 9697704 (mouse model)
Gene classified by Genomics England curator
Rebecca Foulger (Genomics England curator)This gene has been classified as Green List (High Evidence).
Set Mode of Inheritance
Rebecca Foulger (Genomics England curator)Mode of inheritance for FOXE1 was changed to BIALLELIC, autosomal or pseudoautosomal
Set publications
Rebecca Foulger (Genomics England curator)Publications for FOXE1 were set to 9697705; 20484477
Set Phenotypes
Rebecca Foulger (Genomics England curator)Phenotypes for FOXE1 were set to congenital hypothyroidism; Bamforth Lazarus syndrome; Hypothyroidism, Thyroidal Or Athyroidal, With Spiky Hair And Cleft Palate, 241850; thyroid agenesis; cleft palate; spiky hair; choanal atresia
Added New Source
Rebecca Foulger (Genomics England curator)FOXE1 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: Eligibility statement prior genetic testing
Set Phenotypes
Rebecca Foulger (Genomics England curator)Phenotypes for gene FOXE1 were set to congenital hypothyroidism; Bamforth Lazarus syndrome; Hypothyroidism, Thyroidal Or Athyroidal, With Spiky Hair And Cleft Palate, 241850
Set Mode of Inheritance
Olivia Niblock (Genomics England Curator)Model of inheritance for gene FOXE1 was set to BIALLELIC, autosomal or pseudoautosomal
Added New Source
Olivia Niblock (Genomics England Curator)FOXE1 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: UKGTN
Added New Source
Olivia Niblock (Genomics England Curator)FOXE1 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Emory Genetics Laboratory
Created
Olivia Niblock (Genomics England Curator)FOXE1 was created by oniblock