Congenital hypothyroidism

Gene: TUBB1

Comment on list classification: Promoted from red to amber. TUBB1 is not associated with congenital hypothyroidism in OMIM or Gene2Phenotype. PMID: 30446499 reported on 3 unrelated families with affected individuals who have different variants in TUBB1.

Family #1: consanguineous family of Algerian descent with 3 out of 5 children affected by disease. All 3 children are homozygous for a missense variant and both parents are heterozygous.

Family #2: Moroccan father and French mother with 1 affected child (3 children in total). The affected child is heterozygous for a nonsense variant. The father has the same heterozygous variant, but no tests could be done to confirm phenotype. A paternal aunt with the same heterozygous variant also presented with disease.

Family #3: French family with 1 affected child (3 children in total). Affected child is heterozygous for a frameshift variant. The father has the same heterozygous variant but has normal thyroid function (did not present with disease).

Knockout mouse model showed a thyroid phenotype.

Due to the evidence from family #2 and #3 it was decided that there was not yet enough evidence to promote TUBB1 to green gene status.

Created: 19 Jun 2019, 1:08 p.m.

I don't know

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Primary congenital hypothyroidism, thyroid dysgenesis, macroplatelets