Congenital hypothyroidism

Gene: DUOX2

Green List (high evidence)

DUOX2 (dual oxidase 2)
EnsemblGeneIds (GRCh38): ENSG00000140279
EnsemblGeneIds (GRCh37): ENSG00000140279
OMIM: 606759, Gene2Phenotype
DUOX2 is in 1 panel

2 reviews

Rebecca Foulger (Genomics England curator)

PMID:27166716 (Matsuo et al., 2016) report 14 DUOX2 variants in 11 patients. One patient had digenic heterozygous variants of both DUOX2 and TPO.
Created: 16 Feb 2017, 4:55 p.m.
Comment on list classification: Updated rating from Amber to Green: Rated green by reviewer. 3 cases in OMIM reporting homozygous (and 1 heterozygous) mutations in DUOX2 in unrelated patients with hypothyroidism. Plus many more cases reported in literature.
Created: 16 Feb 2017, 4:55 p.m.
'Monogenic-Polygenic' tag is supported by multiple papers listing digenic disease association: PMID:26758695 (Zheng et al., 2015) report a boy with goitrous CH due to a novel splice-site mutation in DUOXA2 (c.554+5C>T) and a missense mutation in DUOX2 (c.2654G>A (p.R885Q). Nicholas et al., 2016 (PMID:27525530) report triallelic (digenic) mutations in DUOX2 and TG (6 cases). PMID:27166716 (Matsuo et al., 2016) report one patient with digenic heterozygous variants of both DUOX2 and TPO.
Created: 16 Feb 2017, 4:53 p.m.
Comment when marking as ready: Green rating from reviewer, biallelic and monoallelic inheritance is supported by reviewer and literature. The literature reports patients from mixed populations (including Italy, Turkey, Netherlands).
Created: 13 Feb 2017, 11:41 a.m.
Paper supporting both biallelic and monoallelic inheritance: PMID:12110737 (Moreno et al., 2002) report one patient with permanent and severe thyroid hormone deficiency with a homozygous nonsense mutation in DUOX2 (THOX2) gene that eliminates all functional domains of the protein. 3 of the 8 patients with mild transient congenital hypothyroidism ahad heterozygous mutations in DUOX2 (THOX2) that prematurely truncate the protein.
Created: 13 Feb 2017, 11:32 a.m.
Comment on mode of inheritance: Updated mode of inheritance from 'biallelic' to 'both monoallelic and biallelic' to match review and literature. A number of papers (PMID:12110737 and PMID:24423310) support that biallelic mutations cause a severe thyroid hormone deficiency, and heterozygous mutations cause mild hypothyroidism.
Created: 13 Feb 2017, 11:31 a.m.

Nadia Schoenmakers (University of Cambridge)

Green List (high evidence)

Permanent or transient CH, often exhibit borderline screening TSH with more marked hypothyroidism at the time of confirmatory venous testing. May have goitre. Usually have partial iodide organification defect if tested.
Created: 11 Feb 2017, 12:17 a.m.
Permanent or transient CH, often exhibit borderline screening TSH with more marked hypothyroidism at the time of confirmatory venous testing. May have goitre.
Created: 11 Feb 2017, 12:05 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
permanent congenital hypothyroidism; transient congenital hypothyroidism; eutopic gland-in-situ; goitre; borderline congenital hypothyroidism; iodide organification defect

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Congenital hypothyroidism
  • Thryoid dyshormonogenesis 6, 607200
  • permanent congenital hypothyroidism
  • transient congenital hypothyroidism
  • eutopic gland-in-situ
  • goitre
  • borderline congenital hypothyroidism
  • iodide organification defect
Tags
monogenic-polygenic
OMIM
606759
Clinvar variants
Variants in DUOX2
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 DUOX2 were set to 12110737; 24423310; 16134168; 27525530 (Nicholas et al.,2016) identify a monogenic and digenic basis of disease; 27166716

16 Feb 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for DUOX2 were set to 12110737; 24423310; 16134168; 27525530 (Nicholas et al.,2016) identify a monogenic and digenic 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 DUOX2 were set to 12110737; 24423310; 16134168

13 Feb 2017, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for DUOX2 were set to Congenital hypothyroidism; Thryoid dyshormonogenesis 6, 607200; permanent congenital hypothyroidism; transient congenital hypothyroidism; eutopic gland-in-situ; goitre; borderline congenital hypothyroidism; iodide organification defect

13 Feb 2017, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for DUOX2 were set to 12110737; 24423310

13 Feb 2017, Gel status: 2

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for DUOX2 was changed to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

23 Jan 2017, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

DUOX2 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 DUOX2 were set to Congenital hypothyroidism; Thryoid dyshormonogenesis 6, 607200

13 Oct 2016, Gel status: 2

Added New Source

Olivia Niblock (Genomics England Curator)

DUOX2 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: UKGTN

13 Oct 2016, Gel status: 0

Created

Olivia Niblock (Genomics England Curator)

DUOX2 was created by oniblock

13 Oct 2016, Gel status: 1

Added New Source

Olivia Niblock (Genomics England Curator)

DUOX2 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Illumina TruGenome Clinical Sequencing Services