Novel Compound Heterozygous Pathogenic Mutations of SLC5A5 in a Chinese Patient With Congenital Hypothyroidism

Defects in the human sodium/iodide symporter ( ) gene have been reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify mutations in Chinese patients with CH and to evaluate the function of the mutation. Two hundred and seventy-three patients with primary CH were screened for mutations in using next-generation sequencing. We investigated the expression and cellular localization of the novel compound heterozygous mutation in . The functional activity of the mutants was further examined . In 273 patients with CH, two previously undescribed pathogenic mutations p.Gly51AlafsTer45 (G51fs) and p.Gly421Arg (G421R) in a compound heterozygous state in were identified in a pediatric patient. G51fs was located in the first intercellular loop connecting transmembrane segment I and II, whereas G421R was in the transmembrane segment (TMS) XI. G51fs and G421R resulted in a truncated NIS and reduced protein expression, respectively. experiments further showed that the normal function of iodine transport of sodium-iodide symporter (NIS) mutants was markedly impaired. The undescribed compound heterozygous mutation of was discovered in a Chinese CH patient. The mutation led to significantly reduced NIS expression and impaired iodide transport function accompanied by the impaired location of the NIS on the plasma membrane. Our study thus provides further insights into the roles of in CH pathogenesis.