Congenital hypothyroidismGene: NKX2-5
Comment on list classification: Updated rating from Red to Amber until further information is available. Comment from Helen Brittain: PMID:16418214 identify 4 cases from 241 cases, but all were inherited from an unaffected parent and one unaffected sibling also carried the mutation. The authors postulate polygenic inheritance.
Created: 14 Feb 2017, 5:35 p.m.
Comment on mode of pathogenicity: PMID:16418214 (Dentice et al., 2006) report a dominant negative mode of action for 3 NKX2-5 mutations in patients with thyroid dysgenesis,
Created: 13 Feb 2017, 5:01 p.m.
Comment on mode of inheritance: Mode of inheritance confirmed by OMIM and G2P.
Created: 13 Feb 2017, 4:56 p.m.
Confirmed DD-G2P gene for 'Hypothyroidism, congenital nongoitrous, 5 (MIM:225250)'.
Created: 13 Feb 2017, 4:55 p.m.
Highly variable penetrance, ambiguity as to whether Nkx2-5 mutations alone cause CH.
Created: 11 Feb 2017, 12:32 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
thyrioid ectopy, thyroid agenesis, congenital heart disease
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 Amber List (Moderate Evidence).
Mode of pathogenicity for NKX2-5 was changed to Other - please provide details in the comments
Phenotypes for NKX2-5 were set to Hypothyroidism, congenital nongoitrous, 5, 225250; thyrioid ectopy, thyroid agenesis, congenital heart disease
Publications for NKX2-5 were set to 16418214
Mode of inheritance for NKX2-5 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
NKX2-5 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: Radboud University Medical Center, Nijmegen
NKX2-5 was created by rfoulger
NKX2-5 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Other