Novel TUBB1 Mutation Related To Thyroid Dysgenesis In 289 Chinese Patients

Objective: We aimed to study the types and characteristics of TUBB1 mutations in a large Chinese cohort with congenital hypothyroidism (CH) and thyroid dysgenesis (TD). Methods: : Mutation of the entire coding region of TUBB1 was analysed by Sanger sequencing in 289 children with CH and TD from China. Functional studies were further used to identify the effect of novel mutations on thyroid cells. Results: : Among the 289 children with CH and TD, 4 (1.4%) had a c.952C>T(p.R318W) heterozygous mutation in TUBB1, resulting in a change from tryptophan to arginine at codon 318 of the TUBB1 protein. Functional studies indicated that the p.R318W mutant decreased TUBB1 expression and inhibited cell proliferation in a human thyroid cell line. Conclusions: : A novel heterozygous missense mutation of TUBB1 in children with CH and TD was identified first in China, laying the foundations to expand the genotype-phenotype spectrum of TD.