Congenital hypothyroidism

Gene: TPO

Comment on publications: PMID: 39890415 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI

Created: 20 Feb 2025, 3:49 p.m. | Last Modified: 20 Feb 2025, 3:49 p.m.

Panel Version: 2.21

monogenic-polygenic tag added based on Nicholas et al., 2016 (PMID:27525530) who report triallelic (digenic) mutations in TG and TPO (1 case) and SLC26A4 and TPO (3 cases), and PMID:27166716 (Matsuo et al., 2016) who report one patient with digenic heterozygous variants of both DUOX2 and TPO.

Created: 16 Feb 2017, 4:55 p.m.

Comment when marking as ready: Rated green by reviewer, and many cases in OMIM and literature of TPO mutations causing CH.

Created: 13 Feb 2017, 1:28 p.m.

Comment on list classification: Updated rating from Amber to Green: 1 Green review plus >3 cases of TPO mutations causing congenital hypothyroidism with iodide organification defect (>29 families reported in PMID:11061528).

Created: 13 Feb 2017, 1:27 p.m.

PMID:11061528 (Bakker et al., 2000) present a Dutch cohort study assessing thyroid peroxidase (TPO) mutations in 45 patients (35 families) with congenital hypothyroidism due to a total iodide organification defect; 16 different mutations were found in 29 families (13 homozygous and 16 compound heterozygous). Additionally, in one family, partial maternal isodisomy of 2p was detected, in four families only one mutated TPO allele could be detected, and in one family no inactivating TPO mutation could be found (in these 5 families additional mutations may be present in non-coding regions).

Created: 13 Feb 2017, 1:25 p.m.

Comment on mode of inheritance: Mode of inheritance confirmed by OMIM.

Created: 13 Feb 2017, 1:08 p.m.

Green List (high evidence)

Iodide organification defect (usually total); may have goitre, usually severe congenital hypothyroidism.

Created: 11 Feb 2017, 12:16 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Iodide organification defect; goitre

Publications

• PMID: 12938097