Congenital hypothyroidism
Gene: SOX3EnsemblGeneIds (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)
Highly variable phenotypeCreated: 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
-
- Mental retardation, X-linked, with isolated growth hormone deficiency, OMIM:300123
- Intellectual disability, X-linked, with panhypopituitarism, MONDO:0010252
- Panhypopituitarism, X-linked, OMIM:312000
- Panhypopituitarism, X-linked, MONDO:0010712
- OMIM
- 313430
- Clinvar variants
- Variants in SOX3
- Penetrance
- Complete
- Publications
- Panels with this gene
History Filter Activity
Set Phenotypes
Arina Puzriakova (Genomics England Curator)Phenotypes for gene: SOX3 were changed from GH,TSH, ACTH, LH, FSH deficiency, variable mental retardation, undescended posterior pituitary, anterior pituitary hypoplasia, or persistence of the craniopharyngeal canal to Mental retardation, X-linked, with isolated growth hormone deficiency, OMIM:300123; Intellectual disability, X-linked, with panhypopituitarism, MONDO:0010252; Panhypopituitarism, X-linked, OMIM:312000; Panhypopituitarism, X-linked, MONDO:0010712
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.
Gene classified by Genomics England curator
Rebecca Foulger (Genomics England curator)This gene has been classified as Red List (Low Evidence).
Set publications
Rebecca Foulger (Genomics England curator)Publications for SOX3 were set to 12428212; 15800844; 26416826 (2015 review)
Set publications
Rebecca Foulger (Genomics England curator)Publications for SOX3 were set to 12428212
Added New Source
Nadia Schoenmakers (University of Cambridge)SOX3 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Literature
Created
Nadia Schoenmakers (University of Cambridge)SOX3 was created by [email protected]