Congenital hypothyroidism
Gene: HESX1Comment on list classification: Updated rating from Grey to Green: 1 Green review (from gene submitter). Plus >3 cases of HESX1 mutations causing combined pituitary hormone deficiency, which can present with CH. 1 case mentions hypothyroidism specifically (PMID:11136712).Created: 21 Feb 2017, 10:09 a.m.
PMID:11136712 (Thomas et al., 2001) expanded their 1998 paper and scanned for HESX1 mutations in 228 patients with a broad spectrum of congenital pituitary defects. 3 different heterozygous missense mutations were detected in individuals with relatively mild pituitary hypoplasia or SOD, including G18C in individual II.1 who had secondary hypothyroidism from age 7 (low TSH and T4).Created: 21 Feb 2017, 10:07 a.m.
HESX1 is an early pituitary transcription factor. Mutations in early or late pituitary transcription factors may cause central hypothyroidism (CH), a particular hypothyroid condition due to an insufficient stimulation by TSH of an otherwise normal thyroid gland. In these cases, CH does not occur in isolation, but is one of the evolving pituitary hormone deficiencies [PMID:26416826].Created: 21 Feb 2017, 10:03 a.m.
>3 cases of HESX1 mutations causing combined pituitary hormone deficiency (CPHD5; MIM:182230).Created: 20 Feb 2017, 10:44 a.m.
Comment on mode of inheritance: Mode of inheritance supported by OMIM.Created: 20 Feb 2017, 10:23 a.m.
Probable DD-G2P gene for HESX1-related combined pituitary hormone deficiency.Created: 20 Feb 2017, 10:17 a.m.
Variable penetranceCreated: 19 Feb 2017, 9:54 p.m.
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes
Panhypopiuitarism; GH and evolving TSH, ACTH, LH/FSH deficiency, septo-optic dysplasia,anterior pituitary, ectopic posterior pituitary, agenesis of corpus callous, optic nerve hypoplasia
Publications
Phenotypes for gene: HESX1 were changed from Panhypopiuitarism; GH and evolving TSH, ACTH, LH/FSH deficiency; septo-optic dysplasia; anterior pituitary, ectopic posterior pituitary; agenesis of corpus callous; optic nerve hypoplasia; Pituitary hormone deficiency, combined, 5, 182230 to Growth hormone deficiency with pituitary anomalies, OMIM:182230; Pituitary hormone deficiency, combined, 5, OMIM:182230; Septooptic dysplasia, OMIM:182230
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.
Phenotypes for HESX1 were set to Panhypopiuitarism; GH and evolving TSH, ACTH, LH/FSH deficiency; septo-optic dysplasia; anterior pituitary, ectopic posterior pituitary; agenesis of corpus callous; optic nerve hypoplasia; Pituitary hormone deficiency, combined, 5, 182230
This gene has been classified as Green List (High Evidence).
Publications for HESX1 were set to 9620767; 11136712; 26416826 (2015 review)
Mode of inheritance for HESX1 was changed to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for HESX1 were set to Panhypopiuitarism; GH and evolving TSH, ACTH, LH/FSH deficiency, septo-optic dysplasia,anterior pituitary, ectopic posterior pituitary, agenesis of corpus callous, optic nerve hypoplasia; Pituitary hormone deficiency, combined, 5, 182230
Publications for HESX1 were set to 9620767; 11136712
HESX1 was created by [email protected]
HESX1 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Literature