Congenital hypothyroidism
Gene: FOXE1Comment 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.
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.
This gene has been classified as Green List (High Evidence).
Mode of pathogenicity for FOXE1 was changed to Other - please provide details in the comments
Publications for FOXE1 were set to 9697705; 20484477; 9697704 (mouse model); 24219130 (gain-of-function mutation)
Publications for FOXE1 were set to 9697705; 20484477; 9697704 (mouse model); 24219130
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
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
This gene has been classified as Green List (High Evidence).
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
Publications for FOXE1 were set to 9697705; 20484477; 9697704 (mouse model)
This gene has been classified as Green List (High Evidence).
Mode of inheritance for FOXE1 was changed to BIALLELIC, autosomal or pseudoautosomal
Publications for FOXE1 were set to 9697705; 20484477
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
FOXE1 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: Eligibility statement prior genetic testing
Phenotypes for gene FOXE1 were set to congenital hypothyroidism; Bamforth Lazarus syndrome; Hypothyroidism, Thyroidal Or Athyroidal, With Spiky Hair And Cleft Palate, 241850
Model of inheritance for gene FOXE1 was set to BIALLELIC, autosomal or pseudoautosomal
FOXE1 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: UKGTN
FOXE1 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Emory Genetics Laboratory
FOXE1 was created by oniblock