DETECTION OF TUBB1 MUTATIONS FOR DIAGNOSING THYROID DYSGENESIS

摘要

The genetic causes of congenital hypothyroidism due to thyroid dysgenesis (TD) remain largely unknown. The inventors identified three novel TUBB1 gene mutations that co-segregated with TD in three affected families. TUBB1 (Tubulin, Beta 1 Class VI) encodes a member of the β-tubulin protein family. In mice, Tubb1 knock-out in vivo disrupted microtubule integrity by preventing β1-tubulin incorporation and impaired thyroid migration and thyroid hormone secretion. In addition, TUBB1 mutations caused hyperaggregation of human platelets. The data highlight unexpected roles for β1-tubulin in thyroid development and function and in platelet physiology. Accordingly, the present invention relates to a method of diagnosing thyroid dysgenesis in a subject, comprising detecting a mutation in the TUBB1 gene in a sample obtained from said subject, wherein detecting the presence of a mutation in the TUBB1 gene is considered to be indicative of thyroid dysgenesis.