Congenital hypothyroidism

Gene: HESX1

Green List (high evidence)

HESX1 (HESX homeobox 1)
EnsemblGeneIds (GRCh38): ENSG00000163666
EnsemblGeneIds (GRCh37): ENSG00000163666
OMIM: 601802, Gene2Phenotype
HESX1 is in 10 panels

2 reviews

Rebecca Foulger (Genomics England curator)

Comment 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.

Nadia Schoenmakers (University of Cambridge)

Green List (high evidence)

Variable penetrance
Created: 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

  • Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Dattani MT, Martinez-Barbera JP, Thomas PQ, Brickman JM, Gupta R, Mårtensson IL, Toresson H, Fox M, Wales JK, Hindmarsh PC, Krauss S, Beddington RS, Robinson IC. Nat Genet. 1998 Jun
  • 19(2):125-33. Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia. Thomas PQ, Dattani MT, Brickman JM, McNay D, Warne G, Zacharin M, Cameron F, Hurst J, Woods K, Dunger D, Stanhope R, Forrest S, Robinson IC, Beddington RS. Hum Mol Genet. 2001 Jan 1
  • 10(1):39-45.

Details

Mode of Inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
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
  • Pituitary hormone deficiency, combined, 5, 182230
OMIM
601802
Clinvar variants
Variants in HESX1
Penetrance
Incomplete
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.

22 Feb 2017, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

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

21 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).

20 Feb 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for HESX1 were set to 9620767; 11136712; 26416826 (2015 review)

20 Feb 2017, Gel status: 0

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for HESX1 was changed to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

20 Feb 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

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

20 Feb 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for HESX1 were set to 9620767; 11136712

19 Feb 2017, Gel status: 0

Created

Nadia Schoenmakers (University of Cambridge)

HESX1 was created by [email protected]

19 Feb 2017, Gel status: 0

Added New Source

Nadia Schoenmakers (University of Cambridge)

HESX1 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Literature