TY - JOUR AB - Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder with a genetic origin. The purpose of the present study was to analyze the mutation spectrum of CH patients in China. A targeted next‑generation sequencing panel covering all exons of 29 CH‑related causative genes was used in 43 Han Chinese patients with CH [11 dysgenesis and 32 glands in situ (GIS)]. The functional impact and pathogenicity of detected variants were analyzed using a comprehensive bioinformatics approach and co‑segregation studies. A total of 47 rare non‑polymorphic variants in 9 target genes associated with thyroid hormone synthesis (DUOX2, DUOXA2, TPO, TG, SLC26A4 and SLC5A5), thyroid stimulating hormone resistance (TSHR) and central hypothyroidism (PROP1 and TRHR) were identified in 31 patients (31/43, 72%). Of these variants, 8 were novel, including 3 in DUOX2, 2 in TPO, 3 in TSHR and 1 in SLC5A5. Variants were mostly affected by DUOX2, TG, TPO and TSHR. Approximately 44% of the patients (19/43) carried DUOX2 variants. The mutation detection rates in patients with GIS were higher compared with patients with dysgenesis [25/32 (78%) vs. 6/11 (54%)]. Oligogenic mutations were detected in 25.6% of the total cases and 35% of the mutated cases. Genetic basis was ascertained in 13 patients, reaching a diagnosis detection rate of 30%. In conclusion, genetic defects in dyshormonogenesis, mainly in DUOX2, were the main genetic cause of CH in the Chinese population. Oligogenicity is highly involved in CH pathogenesis and may thus be an important factor in common phenotypic variability observed in patients with CH. AD - The National Engineering Research Center for Miniaturized Detection Systems, College of Life Science, Northwest University, Xi'an, Shaanxi 710069, P.R. China The Tianyou Children's Hospital of Xi'an, Xi'an, Shaanxi 710061, P.R. China The Chang An Hospital, Xi'an, Shaanxi 710016, P.R. China Beijing Shijitan Hospital, Beijing 100080, P.R. China Endocrine Department, Xi'an Children's Hospital, Xi'an, Shaanxi 710003, P.R. China AU - Wang,Huijuan AU - Kong,Xiaohong AU - Pei,Yanrui AU - Cui,Xuemei AU - Zhu,Yijie AU - He,Zixuan AU - Wang,Yanxia AU - Zhang,Lirong AU - Zhuo,Lixia AU - Chen,Chao AU - Yan,Xiaoli AU - Wang,Huijuan AU - Kong,Xiaohong AU - Pei,Yanrui AU - Cui,Xuemei AU - Zhu,Yijie AU - He,Zixuan AU - Wang,Yanxia AU - Zhang,Lirong AU - Zhuo,Lixia AU - Chen,Chao AU - Yan,Xiaoli AU - Wang,Huijuan AU - Kong,Xiaohong AU - Pei,Yanrui AU - Cui,Xuemei AU - Zhu,Yijie AU - He,Zixuan AU - Wang,Yanxia AU - Zhang,Lirong AU - Zhuo,Lixia AU - Chen,Chao AU - Yan,Xiaoli AU - Wang,Huijuan AU - Kong,Xiaohong AU - Pei,Yanrui AU - Cui,Xuemei AU - Zhu,Yijie AU - He,Zixuan AU - Wang,Yanxia AU - Zhang,Lirong AU - Zhuo,Lixia AU - Chen,Chao AU - Yan,Xiaoli AU - Wang,Huijuan AU - Kong,Xiaohong AU - Pei,Yanrui AU - Cui,Xuemei AU - Zhu,Yijie AU - He,Zixuan AU - Wang,Yanxia AU - Zhang,Lirong AU - Zhuo,Lixia AU - Chen,Chao AU - Yan,Xiaoli AU - Wang,Huijuan AU - Kong,Xiaohong AU - Pei,Yanrui AU - Cui,Xuemei AU - Zhu,Yijie AU - He,Zixuan AU - Wang,Yanxia AU - Zhang,Lirong AU - Zhuo,Lixia AU - Chen,Chao AU - Yan,Xiaoli AU - Wang,Huijuan AU - Kong,Xiaohong AU - Pei,Yanrui AU - Cui,Xuemei AU - Zhu,Yijie AU - He,Zixuan AU - Wang,Yanxia AU - Zhang,Lirong AU - Zhuo,Lixia AU - Chen,Chao AU - Yan,Xiaoli DA - 2020/07/01 DO - 10.3892/mmr.2020.11078 EP - 309 IS - 1 JO - Mol Med Rep KW - congenital hypothyroidism dyshormonogenesis oligogenicity DUOX2 next‑generation sequencing PY - 2020 SN - 1791-2997 1791-3004 SP - 297 ST - Mutation spectrum analysis of 29 causative genes in 43 Chinese patients with congenital hypothyroidism T2 - Molecular Medicine Reports TI - Mutation spectrum analysis of 29 causative genes in 43 Chinese patients with congenital hypothyroidism UR - https://doi.org/10.3892/mmr.2020.11078 VL - 22 ER -