Congenital hypothyroidism

Gene: TBL1X

Green List (high evidence)

TBL1X (transducin beta like 1 X-linked)
EnsemblGeneIds (GRCh38): ENSG00000101849
EnsemblGeneIds (GRCh37): ENSG00000101849
OMIM: 300196, Gene2Phenotype
TBL1X is in 4 panels

4 reviews

Ivone Leong (Genomics England Curator)

Comment on list classification: Promoted from amber to green based on new evidence provided by Martina Owens (Exeter Genetics Laboratory, Royal Devon and Exeter NHS Foundation Trust).
Created: 17 Jan 2019, 3:06 p.m.

Martina Owens (Exeter Genetics Laboratory, Royal Devon and Exeter NHS Foundation Trust)

Green List (high evidence)

Additional paper: Garcia et al 2019 (PMID 30591955) - De novo truncating variant identified in male patient with central hypothyroidism, hypoacusia, ADHD, gastrointestinal dysmotility, and Chiari malformation type I .
Created: 11 Jan 2019, 1:25 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Publications

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Grey to Amber until more information/publications/cases available: Currently 1 green review (from gene submitter). One 2016 paper (PMID: 27603907) identifying missense mutations in 6 families but genotype:phenotype relationship is unclear.
Created: 16 Feb 2017, 2:48 p.m.
1 paper: PMID:27603907 (Heinen et al., 2016) identify 6 TBL1X missense mutations in 8 patients (6 males) from 6 unrelated families with unexplained congenital central hypothyroidism (CeH). However, 2 unaffected male relatives (in family A and family C) have the mutation. After discussion with Helen Brittain, there is insufficient evidence for the variable absence or presence of the phenotype in males and females within the families tested for an X-linked disorder- skewed X-inactivation may be an explanation.
Created: 14 Feb 2017, 5:21 p.m.
Comment on mode of inheritance: PMID:27603907 (Heinen et al., 2016) identify female carriers without congenital central hypothyroidism (CeH), and 1 female with CeH supporting a hemizgyous mode of inheritance where monoallelic mutations may cause the disease.
Created: 14 Feb 2017, 10:55 a.m.
Added 'missense' tag, since all mutations reported in PMID:27603907 (Heinen et al., 2016) are missense.
Created: 14 Feb 2017, 10:49 a.m.

Nadia Schoenmakers (University of Cambridge)

Green List (high evidence)

May have hearing impairment
Created: 11 Feb 2017, 12:57 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
isolated mild-moderate central hypothyroidism

Publications

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Green
Phenotypes
  • isolated mild-moderate central hypothyroidism
  • Hypothyroidism, congenital, nongoitrous, 8, 301033
Tags
missense
OMIM
300196
Clinvar variants
Variants in TBL1X
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

13 Jan 2020, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: TBL1X were changed from isolated mild-moderate central hypothyroidism to isolated mild-moderate central hypothyroidism; Hypothyroidism, congenital, nongoitrous, 8, 301033

17 Jan 2019, Gel status: 3

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: tbl1x has been classified as Green List (High Evidence).

16 Jan 2019, Gel status: 2

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: TBL1X were set to PMID: 27603907

22 Feb 2017, Gel status: 2

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.

14 Feb 2017, Gel status: 2

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Amber List (Moderate Evidence).

14 Feb 2017, Gel status: 0

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for TBL1X was changed to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

11 Feb 2017, Gel status: 0

Added New Source

Nadia Schoenmakers (University of Cambridge)

TBL1X was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Literature

11 Feb 2017, Gel status: 0

Created

Nadia Schoenmakers (University of Cambridge)

TBL1X was created by [email protected]