Newborn Screening and Molecular Profile of Congenital Hypothyroidism in a Chinese Population

Abstract

To review the characteristics of newborn screening of congenital hypothyroidism (CH), we reviewed the newborn screening data, including the levels of blood spot thyroid-stimulating hormone (TSH), and serum TSH and free thyroxine (FT4), of all newborn infants who accepted the newborn screening program during the last 14 years. In total, 437,342 newborn infants underwent CH screening and 192 infants were diagnosed with CH and the incidence of CH was 1:2278. The positive rate of the initial screening was 0.96%, and the positive predictive value was 4.8%. We also designed a target sequencing panel including 13 causative genes: DUOX2, TG, TPO, TSHR, TTF1, TTF2, PAX8, NKX2-5, GNAS, THRA, TSHB, IYD and SLC5A5, to identify the spectrum and prevalence of disease-causing gene mutations in Chinese CH patients. CH-causing genes were detected by targeted next-generation sequencing in 106 CH infants. A total of 132 mutations were identified in 69 cases (65.1%). Of these 132 mutations, 92 (69.70%), 28 (21.21%), and 12 (9.09%) were related to thyroid dyshormonogenesis, thyroid dysgenesis, and thyrotropin resistance, respectively. Mutations in CH-causing genes were found mainly in DUOX2, TG and TSHR, and DUOX2 is the most gene mutation in Chinese CH patients.

Validity of Six Month L-Thyroxine Dose for Differentiation of Transient or Permanent Congenital Hypothyroidism

“…This was attributed to the fact that the majority of patients were from rural areas and probably have some difficulties in accessing their results of screening as well as in admission to our tertiary pediatric endocrine centre. While in some studies, a female predominance has been reported, some others, showed a male predominance ( 8 , 9 , 10 , 11 , 12 , 13 , 14 ). In the present study, there was a slight female predominance.…”

Familial Aggregation of Endemic Congenital Hypothyroidism Syndrome in Congo (DR): Historical Data

“…When looking at the evolution of knowledge in sporadic neonatal hypothyroidism, most of the cases with dysgenesis (aplasia, hypoplasia, and ectopic gland) could not be associated with a specific genetic/metabolic defect—despite the tremendous effort to identify some common metabolic pathway defect in thyroid development. The general concept is that, besides exceptions, sporadic CH with dysgenesis is associated with multifactorial multigenic diversity of genetic or epigenetic [ 28 ] defects with low incidence in the population [ 29 , 30 , 31 ]. By contrast, the present results obtained by the familial aggregation analysis suggest that endemic CH may be in part also of genetic origin—in case of severe iodine deficiency, the data highlighted aggregation at an elevated prevalence in at least two families of the cohort.…”

A global perspective on newborn congenital hypothyroidism screening

“…16 Despite these challenges, a recent study in China examining 437,342 newborns using TSH screening methods with molecular profile was able to detect several mutations, including DUOX2, TG, and TSHR, involved in CH in the Chinese population. 19 The combination of molecular techniques may help clinicians identify high-risk infants for CH based upon specific molecular profiles associated with different ethnic groups. 19 Furthermore, the incorporation of readily available molecular techniques may provide an additional method for confirming and assessing the course of treatment for premature infants or infants presenting with subclinical hypothyroidism.…”

“…19 The combination of molecular techniques may help clinicians identify high-risk infants for CH based upon specific molecular profiles associated with different ethnic groups. 19 Furthermore, the incorporation of readily available molecular techniques may provide an additional method for confirming and assessing the course of treatment for premature infants or infants presenting with subclinical hypothyroidism. 19 Overall, further research is required to determine which methods or technologies may provide insight into reducing or eliminating factors to differentiate patients based on ethnicity, gender, and medical history.…”

“…19 Furthermore, the incorporation of readily available molecular techniques may provide an additional method for confirming and assessing the course of treatment for premature infants or infants presenting with subclinical hypothyroidism. 19 Overall, further research is required to determine which methods or technologies may provide insight into reducing or eliminating factors to differentiate patients based on ethnicity, gender, and medical history. TSH cutoffs for CH screening differ among local, national, and international regions across the globe.…”