Congenital hypothyroidism

Gene: LHX4

Green List (high evidence)

LHX4 (LIM homeobox 4)
EnsemblGeneIds (GRCh38): ENSG00000121454
EnsemblGeneIds (GRCh37): ENSG00000121454
OMIM: 602146, Gene2Phenotype
LHX4 is in 9 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 LHX4 mutations causing combined pituitary hormone deficiency, which can present with CH. Confirmed DD-G2P gene. At least 1 case mentions hypothyroidism specifically (PMID:25955177).
Created: 21 Feb 2017, 10:33 a.m.
LHX4 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, 10:29 a.m.
>3 cases of LHX4 mutations causing Pituitary hormone deficiency, combined, 4 (MIM:262700).
Created: 20 Feb 2017, 11:16 a.m.
Confirmed DD-G2P gene for LHX4-related combined pituitary hormone deficiency.
Created: 20 Feb 2017, 11:10 a.m.

Nadia Schoenmakers (University of Cambridge)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
GH, TSH, ACTH, variable gonadotrophin deficiencies, cerebellar abnormalities, anterior pituitary hypoplasia, etopic posterior pituitary

Publications

  • Syndromic short stature in patients with a germline mutation in the LIM homeobox LHX4. Machinis K, Pantel J, Netchine I, Léger J, Camand OJ, Sobrier ML, Dastot-Le Moal F, Duquesnoy P, Abitbol M, Czernichow P, Amselem S. Am J Hum Genet. 2001 Nov
  • 69(5):961-8.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
Phenotypes
  • GH, TSH, ACTH, variable gonadotrophin deficiencies
  • cerebellar abnormalities
  • anterior pituitary hypoplasia
  • etopic posterior pituitary
  • Pituitary hormone deficiency, combined, 4, 262700
OMIM
602146
Clinvar variants
Variants in LHX4
Penetrance
Complete
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 LHX4 were set to GH, TSH, ACTH, variable gonadotrophin deficiencies; cerebellar abnormalities; anterior pituitary hypoplasia; etopic posterior pituitary; Pituitary hormone deficiency, combined, 4, 262700

21 Feb 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for LHX4 were set to 11567216; 26416826 (2015 review); 25955177

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 LHX4 were set to 11567216; 26416826 (2015 review)

20 Feb 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for LHX4 were set to GH, TSH, ACTH, variable gonadotrophin deficiencies, cerebellar abnormalities, anterior pituitary hypoplasia, etopic posterior pituitary; Pituitary hormone deficiency, combined, 4, 262700

19 Feb 2017, Gel status: 0

Added New Source

Nadia Schoenmakers (University of Cambridge)

LHX4 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Literature

19 Feb 2017, Gel status: 0

Created

Nadia Schoenmakers (University of Cambridge)

LHX4 was created by [email protected]