Congenital hypothyroidism

Gene: SLC26A4

Green List (high evidence)

SLC26A4 (solute carrier family 26 member 4)
EnsemblGeneIds (GRCh38): ENSG00000091137
EnsemblGeneIds (GRCh37): ENSG00000091137
OMIM: 605646, Gene2Phenotype
SLC26A4 is in 4 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 SLC26A4 and TPO (3 cases).
Created: 16 Feb 2017, 4:42 p.m.
Comment when marking as ready: Rated green plus >3 cases.
Created: 14 Feb 2017, 5:31 p.m.
Comment on list classification: Updated rating from Red to Green: 1 green review plus >3 unrelated cases of SLC26A4 causing Pendred syndrome (PDS, MIM:274600). Although the deafness phenotype of PDS may present first, Helen Brittain notes that phenotype variability is recognised and therefore including it on the panel for the minority of cases that may have a milder but progressive hearing component.
Created: 14 Feb 2017, 5:30 p.m.
Added 'treatable' tag based on Reviewer comment and PMID:21543982: Nutritional iodide intake is an important modifier of the thyroid phenotype in Pendred syndrome. With sufficient dietary iodide, about 90% of patients are clinically and biochemically euthyroid (normal thyroid function). In the remaining 10% with elevated TSH level, goiter is always present.
Created: 13 Feb 2017, 4:30 p.m.
PMID:17876604 (Banghova et al., 2008) note that hypothyroidism in Pendred syndrome can (albeit rarely) be present from birth. They investigated 197 Czech Caucasian children with CH detected by the neonatal screening in 1985-2005. They find 2 patients compound heterozygous for SLC26A4.
Created: 13 Feb 2017, 4:18 p.m.
Comment on mode of inheritance: Mode of inheritance confirmed by OMIM.
Created: 13 Feb 2017, 4:06 p.m.

Nadia Schoenmakers (University of Cambridge)

Green List (high evidence)

Often euthyroid if iodine replete.
Created: 11 Feb 2017, 12:38 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Sensorineural deafness; enlarged vestibular aqueduct; Mondini defect; partial iodide organification defect; goitre; mild hypothyroidism

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • Other
Phenotypes
  • Pendred syndrome, 274600 (congenital deafness and thyroid goitre)
  • Sensorineural deafness
  • enlarged vestibular aqueduct
  • Mondini defect
  • partial iodide organification defect
  • goitre
  • mild hypothyroidism
Tags
treatable monogenic-polygenic
OMIM
605646
Clinvar variants
Variants in SLC26A4
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.

14 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).

14 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 Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for SLC26A4 were set to Pendred syndrome, 274600 (congenital deafness and thyroid goitre); Sensorineural deafness; enlarged vestibular aqueduct; Mondini defect; partial iodide organification defect; goitre; mild hypothyroidism

13 Feb 2017, Gel status: 0

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for SLC26A4 was changed to BIALLELIC, autosomal or pseudoautosomal

13 Feb 2017, Gel status: 0

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for SLC26A4 was changed to BIALLELIC, autosomal or pseudoautosomal

13 Feb 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for SLC26A4 were set to 9398842; 11932316

13 Feb 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for SLC26A4 were set to Pendred syndrome, 274600 (diffuse thyroid enlargement (goiter)); Sensorineural deafness; enlarged vestibular aqueduct; Mondini defect; partial iodide organification defect; goitre; mild hypothyroidism

23 Jan 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

SLC26A4 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: Eligibility statement prior genetic testing

23 Jan 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

SLC26A4 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Other

23 Jan 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

SLC26A4 was created by rfoulger