Congenital hypothyroidism
Gene: DUOX2PMID: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.
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
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.
Publications for DUOX2 were set to 12110737; 24423310; 16134168; 27525530 (Nicholas et al.,2016) identify a monogenic and digenic basis of disease; 27166716
Publications for DUOX2 were set to 12110737; 24423310; 16134168; 27525530 (Nicholas et al.,2016) identify a monogenic and digenic basis of disease.
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Publications for DUOX2 were set to 12110737; 24423310; 16134168
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
Publications for DUOX2 were set to 12110737; 24423310
Mode of inheritance for DUOX2 was changed to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
DUOX2 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: Eligibility statement prior genetic testing
Phenotypes for gene DUOX2 were set to Congenital hypothyroidism; Thryoid dyshormonogenesis 6, 607200
DUOX2 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: UKGTN
DUOX2 was created by oniblock
DUOX2 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Illumina TruGenome Clinical Sequencing Services