Congenital hypothyroidism

Gene: SOX3

Red List (low evidence)

SOX3 (SRY-box 3)
EnsemblGeneIds (GRCh38): ENSG00000134595
EnsemblGeneIds (GRCh37): ENSG00000134595
OMIM: 313430, Gene2Phenotype
SOX3 is in 11 panels

2 reviews

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Grey to Red. 1 Green review (by gene submitter). Listed as red after internal clinical discussion: the cases in Woods include a poly-Alanine repeat and a benign missense variant. The disease mainly seems to be caused by gene duplication. The hypopituitary deficiency genes may be beyond the scope of this panel, with hypothyroidism as a less prominent factor.
Created: 22 Feb 2017, 10:34 a.m.
Added the 'gene-duplication' tag based on the X-linked gene duplications reported in PMID:15800844 and PMID:15342697.
Created: 22 Feb 2017, 10:29 a.m.
Solomon et al., 2004 (PMID:15342697) use genomic hybridization to analyse 3 families with hypopituitarism. The proband in family B presents with secondary hypothyroidism. They identify Xq26-q27 duplications in the 3 families. This takes the count of duplications in X-linked hypopituitarism kindreds to 5.
Created: 22 Feb 2017, 10:27 a.m.
Woods et al, 2005 (PMID:15800844) analysed SOX3 mutations among patients with hypopituitarism. They found 3 cases:
(i) a submicroscopic duplication of Xq27.1 (685.6kb) containing the SOX3 gene in 2 siblings with variable hypopituitarism (amongst other symptoms).
(ii) A 7 alanine expansion within a polyalanine tract in SOX3 due to 21bp duplication, in 3 male siblings,
(iii) An A43T variation in SOX3 in another child with hypopituitarism; this variant is classified as benign in ClinVar.
Created: 22 Feb 2017, 10:15 a.m.

Nadia Schoenmakers (University of Cambridge)

Green List (high evidence)

Highly variable phenotype
Created: 19 Feb 2017, 10:05 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
GH,TSH, ACTH, LH, FSH deficiency, variable mental retardation, undescended posterior pituitary, anterior pituitary hypoplasia, or persistence of the craniopharyngeal canal

Publications

  • Laumonnier F, Ronce N, Hamel BC, Thomas P, Lespinasse J, Raynaud M, Paringaux C, Van Bokhoven H, Kalsheuer V, Fryns JP et al. 2002 Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency. American Journal of Human Genetics 71 1450–1455

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Red
Phenotypes
  • GH,TSH, ACTH, LH, FSH deficiency, variable mental retardation, undescended posterior pituitary, anterior pituitary hypoplasia, or persistence of the craniopharyngeal canal
OMIM
313430
Clinvar variants
Variants in SOX3
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

22 Feb 2017, Gel status: 1

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: 1

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Red List (Low Evidence).

20 Feb 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for SOX3 were set to 12428212; 15800844; 26416826 (2015 review)

20 Feb 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for SOX3 were set to 12428212

19 Feb 2017, Gel status: 0

Added New Source

Nadia Schoenmakers (University of Cambridge)

SOX3 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Literature

19 Feb 2017, Gel status: 0

Created

Nadia Schoenmakers (University of Cambridge)

SOX3 was created by [email protected]