Congenital hypothyroidismGene: SOX3
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.
Highly variable phenotype
Created: 19 Feb 2017, 10:05 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
GH,TSH, ACTH, LH, FSH deficiency, variable mental retardation, undescended posterior pituitary, anterior pituitary hypoplasia, or persistence of the craniopharyngeal canal
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
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.
This gene has been classified as Red List (Low Evidence).
Publications for SOX3 were set to 12428212; 15800844; 26416826 (2015 review)
Publications for SOX3 were set to 12428212
SOX3 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Literature
SOX3 was created by [email protected]