Congenital hypothyroidism

Gene: FOXE1

Green List (high evidence)

FOXE1 (forkhead box E1)
EnsemblGeneIds (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.

Nadia Schoenmakers (University of Cambridge)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
thyroid agenesis; cleft palate; spiky hair; choanal atresia

Publications

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

22 Feb 2017, Gel status: 4

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.

13 Feb 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

13 Feb 2017, Gel status: 4

Set mode of pathogenicity

Rebecca Foulger (Genomics England curator)

Mode of pathogenicity for FOXE1 was changed to Other - please provide details in the comments

13 Feb 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for FOXE1 were set to 9697705; 20484477; 9697704 (mouse model); 24219130 (gain-of-function mutation)

13 Feb 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for FOXE1 were set to 9697705; 20484477; 9697704 (mouse model); 24219130

13 Feb 2017, Gel status: 4

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

13 Feb 2017, Gel status: 4

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

13 Feb 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

13 Feb 2017, Gel status: 4

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

13 Feb 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for FOXE1 were set to 9697705; 20484477; 9697704 (mouse model)

13 Feb 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

13 Feb 2017, Gel status: 2

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for FOXE1 was changed to BIALLELIC, autosomal or pseudoautosomal

13 Feb 2017, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for FOXE1 were set to 9697705; 20484477

13 Feb 2017, Gel status: 2

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

23 Jan 2017, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

FOXE1 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: Eligibility statement prior genetic testing

23 Jan 2017, Gel status: 2

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

13 Oct 2016, Gel status: 2

Set Mode of Inheritance

Olivia Niblock (Genomics England Curator)

Model of inheritance for gene FOXE1 was set to BIALLELIC, autosomal or pseudoautosomal

13 Oct 2016, Gel status: 2

Added New Source

Olivia Niblock (Genomics England Curator)

FOXE1 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: UKGTN

13 Oct 2016, Gel status: 1

Added New Source

Olivia Niblock (Genomics England Curator)

FOXE1 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Emory Genetics Laboratory

13 Oct 2016, Gel status: 0

Created

Olivia Niblock (Genomics England Curator)

FOXE1 was created by oniblock