ESPE Abstracts

Background: Congenital hypothyroidism (CH) is a condition that characterize by the deficiency in thyroid hormone. CH has a proximate prevalence of one in 4 000 newborns. Major CH cases were reported to be linked with mutations in TSHR, PAX8, NKX2.1, NKX2.5 and FOXE1 genes.

Objective and hypotheses: The clinical presentation of CH patients caused by PAX8 mutations are variable and PAX8 mutation rates differ significantly among different populations. This study was set to examine the PAX8 mutation spectrum and prevalence among Zhuang Chinese CH patients.

Method: Peripheral venous blood samples were collected from the patients. Genomic DNA was extracted from peripheral blood leukocytes. The PAX8 gene were PCR-amplified with intronic primers covering all the exons and intron-exon boundaries.

Results: Sequence analysis of PAX8 in 378 CH patients revealed five different mutations in nine individuals (two are siblings). The mutations included two known missense variants, namely c.92G>A (p.R31H) and c.91C>T (p.R31C), and one novel missense variant c.68G>T (p.G23V), as well as two novel nonsense variants c.1090C>T (p. R364X) and c.658C>T (p.R220X). The p. R31H mutation is highly recurrent in our patient population but the clinical phenotypes vary a lot among those carried this mutation. PAX8 mutations were mainly associated with permanent CH.

Conclusion: The prevalence of PAX8 mutations was 2.38% among Zhuang Chinese. Our study expanded the PAX8 mutation spectrum and provided the best estimation of mutation rate for Zhuang Chinese CH patients.

Funding: This study was supported by the National Natural Science Foundation of China (81260126), Key Projects of Guangxi Health Department (2012025) and Guangxi Natural Science Foundation Program (2012GXNSFAA053174).