TUBB1 mutations cause thyroid dysgenesis associated with abnormal platelet physiology

ABSTRACT: The genetic causes of congenital hypothyroidism due to thyroid dysgenesis (TD) remain largely unknown. We identified three novel TUBB1 gene mutations that co-segregated with TD in three distinct families leading to 1.1% of TUBB1 mutations in TD study cohort. TUBB1 (Tubulin, Beta 1 Class VI) encodes for a member of the β−tubulin protein family. TUBB1 gene is expressed in the developing and adult thyroid in humans and mice. All three TUBB1 mutations lead to nonfunctional α/ß-tubulin dimers that cannot be incorporated into microtubules. In mice, Tubb1 knock-out disrupted microtubule integrity by preventing β1-tubulin incorporation and impaired thyroid migration and thyroid hormone secretion. In addition, TUBB1 mutations caused the formation of macroplatelets and hyperaggregation of human plat

SUBMITTER: Dr. Athanasia STOUPA 

PROVIDER: S-SCDT-EMM-2018-09569 | biostudies-other |

REPOSITORIES: biostudies-other