Congenital hypothyroidism

Gene: LHX3

Green List (high evidence)

LHX3 (LIM homeobox 3)
EnsemblGeneIds (GRCh38): ENSG00000107187
EnsemblGeneIds (GRCh37): ENSG00000107187
OMIM: 600577, Gene2Phenotype
LHX3 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 LHX3 mutations causing combined pituitary hormone deficiency, which can present with CH. At least 2 cases mention hypothyroidism specifically (PMID:21249393 and PMID:18407919).
Created: 21 Feb 2017, 10:26 a.m.
LHX3 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, 10:10 a.m.
Comment on mode of inheritance: Mode of inheritance confirmed by OMIM and G2P.
Created: 20 Feb 2017, 10:57 a.m.
>3 cases of LHX3 mutations causing MIM:221750 (Pituitary hormone deficiency, combined, 3).
Created: 20 Feb 2017, 10:55 a.m.
Confirmed DD-G2P gene for MIM:221750 (Pituitary hormone deficiency, combined, 3).
Created: 20 Feb 2017, 10:52 a.m.

Nadia Schoenmakers (University of Cambridge)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
GH, TSH, LH, FSH, PRL deficiency, limited neck rotation, short cervical spine, sensorineural deafness, anterior pituitary may be normal, hypoplastic or enlarged

Publications

  • Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency. Netchine I, Sobrier ML, Krude H, Schnabel D, Maghnie M, Marcos E, Duriez B, Cacheux V, Moers Av, Goossens M, Grüters A, Amselem S. Nat Genet. 2000 Jun
  • 25(2):182-6.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • GH, TSH, LH, FSH, PRL deficiency
  • limited neck rotation
  • short cervical spine
  • sensorineural deafness
  • anterior pituitary may be normal, hypoplastic or enlarged
  • Pituitary hormone deficiency, combined, 3, 221750
OMIM
600577
Clinvar variants
Variants in LHX3
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 LHX3 were set to GH, TSH, LH, FSH, PRL deficiency; limited neck rotation; short cervical spine; sensorineural deafness; anterior pituitary may be normal, hypoplastic or enlarged; Pituitary hormone deficiency, combined, 3, 221750

21 Feb 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for LHX3 were set to 10835633; 26416826 (2015 review); 21249393;18407919

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).

21 Feb 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for LHX3 were set to 10835633; 26416826 (2015 review); 21249393

20 Feb 2017, Gel status: 0

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for LHX3 was changed to BIALLELIC, autosomal or pseudoautosomal

20 Feb 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for LHX3 were set to GH, TSH, LH, FSH, PRL deficiency, limited neck rotation, short cervical spine, sensorineural deafness, anterior pituitary may be normal, hypoplastic or enlarged; Pituitary hormone deficiency, combined, 3, 221750

20 Feb 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for LHX3 were set to 10835633; 26416826 (2015 review)

19 Feb 2017, Gel status: 0

Added New Source

Nadia Schoenmakers (University of Cambridge)

LHX3 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Literature

19 Feb 2017, Gel status: 0

Created

Nadia Schoenmakers (University of Cambridge)

LHX3 was created by [email protected]