Congenital hypothyroidism

Gene: LHX3

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.

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.