Congenital hypothyroidism

Gene: TPO

Green List (high evidence)

TPO (thyroid peroxidase)
EnsemblGeneIds (GRCh38): ENSG00000115705
EnsemblGeneIds (GRCh37): ENSG00000115705
OMIM: 606765, Gene2Phenotype
TPO is in 2 panels

2 reviews

Rebecca Foulger (Genomics England curator)

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.

Nadia Schoenmakers (University of Cambridge)

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Congenital hypothyroidism
  • Thyroid dyshormonogenesis 2A, 274500
  • TDH2A
  • Iodide organification defect
  • goitre
Tags
monogenic-polygenic
OMIM
606765
Clinvar variants
Variants in TPO
Penetrance
Complete
Publications
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.

16 Feb 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for TPO were set to 12938097; 8027236; 8964831; 11061528; 27525530 (Nicholas et al.,2016) identify a monogenic basis of disease.

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

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 publications

Rebecca Foulger (Genomics England curator)

Publications for TPO were set to 12938097; 8027236; 8964831; 11061528

13 Feb 2017, Gel status: 2

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

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

13 Feb 2017, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for TPO were set to 12938097

13 Feb 2017, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for TPO were set to Congenital hypothyroidism; Thyroid dyshormonogenesis 2A, 274500; TDH2A; Iodide organification defect; goitre

23 Jan 2017, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

TPO 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 TPO were set to Congenital hypothyroidism; Thyroid dyshormonogenesis 2A, 274500; TDH2A

13 Oct 2016, Gel status: 2

Added New Source

Olivia Niblock (Genomics England Curator)

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

13 Oct 2016, Gel status: 1

Added New Source

Olivia Niblock (Genomics England Curator)

TPO was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Illumina TruGenome Clinical Sequencing Services

13 Oct 2016, Gel status: 0

Created

Olivia Niblock (Genomics England Curator)

TPO was created by oniblock