Congenital hypothyroidism
Gene: TBL1XComment 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.
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
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.
May have hearing impairmentCreated: 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
Phenotypes for gene: TBL1X were changed from isolated mild-moderate central hypothyroidism to isolated mild-moderate central hypothyroidism; Hypothyroidism, congenital, nongoitrous, 8, 301033
Gene: tbl1x has been classified as Green List (High Evidence).
Publications for gene: TBL1X were set to PMID: 27603907
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.
This gene has been classified as Amber List (Moderate Evidence).
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)
TBL1X was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Literature
TBL1X was created by [email protected]