Congenital hypothyroidism
Gene: DUOXA2Comment 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.
Mild permanent or transient CHCreated: 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
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.
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
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Publications for DUOXA2 were set to 18042646; 21367925; 28100324; 26758695;27349010
Mode of inheritance for DUOXA2 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for DUOXA2 were set to 18042646; 21367925; 28100324
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
Publications for DUOXA2 were set to 18042646; 21367925
DUOXA2 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Other
DUOXA2 was created by rfoulger