Familial hypoparathyroidism

Gene: TBX1

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 6 Dec 2024, 1:11 p.m. | Last Modified: 6 Dec 2024, 1:11 p.m.

Panel Version: 2.17

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: There is sufficient evidence to promote this gene to Green on this panel (at least three cases of parathyroid dysfunction, including a patient with isolated hypoparathyroidism) at the next GMS panel update.

Created: 14 Mar 2023, 12:11 p.m. | Last Modified: 14 Mar 2023, 12:11 p.m.

Panel Version: 2.10

TBX1 is encompassed by a region deleted in DiGeorge syndrome (22q11.2). There is some, albeit more limited, evidence linking SNVs with overlapping phenotypes.

Yagi et al 2003 (PMID: 14585638) found three cases with conotruncal anomaly face syndrome or DiGeorge's syndrome including velopharyngeal insufficiency of the cleft palate and/or thymus and parathyroid abnormalities but no cognitive deficits. Zweier et al., 2007 (PMID: 17273972) reported a heterozygous missense variant in a familial case of Shprintzen syndrome and Li et al., 2018 (PMID: 30137364) described two families with splice-altering variants in whom phenotypes ranged from isolated hypoparathyroidism (with reduced penetrance) to hypoparathyroidism with additional DiGeorge sequence-like features.

Also details about an addition case at NWGLH provided by Ronnie Wright on R15 panel. Patient harbouring a de novo final exon frameshift variant referred via immunology clinician and has clinical diagnosis of DiGeorge syndrome, including hypoparathyroidism (prior 22q11 deletion testing negative).

Created: 14 Mar 2023, 12:09 p.m. | Last Modified: 14 Mar 2023, 12:09 p.m.

Panel Version: 2.7

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
DiGeorge syndrome, OMIM:188400; Conotruncal anomaly face syndrome, OMIM:217095; Velocardiofacial syndrome, OMIM:192430

Publications

• 14585638
• 17273972
• 30137364

Comment on list classification: PMID: 30137364 reports on 2 unrelated families who have hypoparathyroidism and have splice variants in the TBX1 gene that leads to exon skipping. This suggests that TBX1 may have a role in hypoparathyroidism as stated in Treena Cranston's (Oxford) review.

Created: 10 Jan 2019, 2:37 p.m.

Red List (low evidence)

Red evidence to date but recent publication of this gene (PMID: 30137364) showing association with isolated hypoparathyroidism. Too early for diagnostic panels but of interest for research, so flagging for future consideration
Sources: Other

Created: 9 Jan 2019, 7:02 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• PMID: 30137364