Mutation screening of eight genes and comparison of the clinical data in a Chinese cohort with congenital hypothyroidism

Abstract Background Congenital hypothyroidism (CH) is a common neonatal endocrine disorder, characterized by irreversible intellectual disability and short stature if left untreated. It can be divided into thyroid dysgenesis (TD), including athyreosis, ectopy and hypoplasia, and dyshormonogenesis (DH), also referring to gland in situ (GIS), in which patients have eutopic thyroids with normal size or goiter. This study aims to analyze the clinical and genetic data of the 606 patients with TD or GIS, and to explore the mutation frequencies of the eight genes and the inheritance pattern of CH. Methods Targeted next generation sequencing (NGS) and statistical analysis were performed for mutation screening on eight CH-related genes and the comparison of clinical data in a cohort of 606 Chinese CH patients from Henan Province. Results A total of 208 variants were detected in genes required for thyroid formation ( TSHR , GLIS3 , BOREALIN , NTN1 , JAG1 and TUBB1 ) and thyroid hormone synthesis ( TG and TPO ) in 167 subjects. Monogenic variants were the most prevalent with a percentage of 73.56% (153/208) followed by digenic variants (24.52%, 51/208) and oligogenic variants (1.92%, 4/208). However, no differences were found in various clinical data between patients with and without variants, as well as between patients with monogenic variants and non-monogenic variants. Conclusions Our results suggested that apart from Mendelian monogenic inheritance, digenic and oligogenic inheritance of CH could not be excluded and also involves other factors, such as penetrance, epigenetic mechanisms and environmental factors.