Congenital hypothyroidism

Gene: DUOXA2

Green List (high evidence)

DUOXA2 (dual oxidase maturation factor 2)
EnsemblGeneIds (GRCh38): ENSG00000140274
EnsemblGeneIds (GRCh37): ENSG00000140274
OMIM: 612772, Gene2Phenotype
DUOXA2 is in 2 panels

2 reviews

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Red to Green: 1 green review plus >3 monogenic cases (from OMIM and additional literature) plus additional polygenic case.
Created: 16 Feb 2017, 4:59 p.m.
'Monogenic-Polygenic' tag is supported by PMID:26758695 (Zheng et al., 2015) who 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).
Created: 16 Feb 2017, 4:58 p.m.
Added 'deletions' tag based on PMID:21367925 (Hulur et al., 2011) who report a German patient presenting with an elevated TSH and enlarged thyroid gland at neonatal screening. The patient has a missense mutation (C189R) on the maternal DUOXA2 allele, and a deletion on the other allele encompassing DUOX2, DUOXA1, and DUOXA2. Therefore the patient also lacks one allele of DUOX2 and DUOXA1.
Created: 14 Feb 2017, 3:48 p.m.
Comment when marking as ready: Green review plus >3 monogenic (and additional polygenic) cases.
Created: 13 Feb 2017, 2:18 p.m.
PMID:27349010 (Yang et al., 2016): Dizygotic twins diagnosed with CH at neonatal screening. Each harbored a single heterozygous mutation in either the DUOXA2 or the DUOX2 gene: DUOXA2 c.738C>G (p.Y246X) in the boy and DUOX2 c.2654G>A (p.R885Q) in the girl. The girl was more severe in several aspects than her brother. Germline mutations were consistent with autosomal recessive inheritance.
Created: 13 Feb 2017, 2:09 p.m.
Comment on mode of inheritance: Changed Mode of inheritance from 'biallelic' to 'both biallelic and monoallelic'. This MOI is supported by the Reviewer, and literature. PMID:28100324 (Tan et al., 2017) show that 2 patients with the p.Y246X homozygous mutation had transient and mild permanent CH. Among the 4 patients with a heterozygous mutation, the p.Y246X carrier manifested as typical permanent CH, and the other three were manifested as transient CH.
Created: 13 Feb 2017, 2:03 p.m.
PMID:28100324 (Tan et al., 2017) present further cases supporting the DUOXA2:hypothyroidism association: among 20 CH patients, 2 had p.Y246X homozygous mutations, 4 had a heterozygous mutation (2 carried the known pathogenic mutation c.413-414insA, 1 carried p.Y246X, and 1 carried a novel mutation, p.G79R).
Created: 13 Feb 2017, 2:01 p.m.
PMID:18042646 (Zamproni et al., 2008) report 1 Chinese patient with CH who was homozygous for a nonsense mutation (p.Y246X) in DUOXA2. Biallelic inheritance reported since heterozygous carriers had normal thyroid function. One heterozygous carrier of Y246X was identified in unrelated Chinese controls.
Created: 13 Feb 2017, 1:45 p.m.

Nadia Schoenmakers (University of Cambridge)

Green List (high evidence)

Mild permanent or transient CH
Created: 11 Feb 2017, 12:21 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
eutopic gland-in-situ, mild congenital hypothyroidism, transient congenital hypothyroidism

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Thyroid dyshormonogenesis 5, 274900
  • HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 5
  • eutopic gland-in-situ
  • mild congenital hypothyroidism
  • transient congenital hypothyroidism
Tags
deletions monogenic-polygenic
OMIM
612772
Clinvar variants
Variants in DUOXA2
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.

22 Feb 2017, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for DUOXA2 were set to Thyroid dyshormonogenesis 5, 274900; HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 5; eutopic gland-in-situ; mild congenital hypothyroidism; transient congenital hypothyroidism

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: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for DUOXA2 were set to 18042646; 21367925; 28100324; 26758695;27349010

13 Feb 2017, Gel status: 0

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for DUOXA2 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

13 Feb 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for DUOXA2 were set to 18042646; 21367925; 28100324

13 Feb 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for DUOXA2 were set to Thyroid dyshormonogenesis 5, 274900; HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 5; eutopic gland-in-situ, mild congenital hypothyroidism, transient congenital hypothyroidism

13 Feb 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for DUOXA2 were set to 18042646; 21367925

23 Jan 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

DUOXA2 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Other

23 Jan 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

DUOXA2 was created by rfoulger