scholarly journals Targeted next-generation sequencing of thirteen causative genes in Chinese patients with congenital hypothyroidism

2018 ◽  
Vol 65 (10) ◽  
pp. 1019-1028 ◽  
Author(s):  
Wei Long ◽  
Guanting Lu ◽  
Wenbai Zhou ◽  
Yuqi Yang ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Congenital Hypothyroidism ◽  
Chinese Patients ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

scholarly journals The genetic analysis of Chinese patients with clonal cytopenias using targeted next-generation sequencing

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lijuan Zhang ◽  
YuYe Shi ◽  
Yue Chen ◽  
Shandong Tao ◽  
Wenting Shi ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Myelodysplastic Syndromes ◽  
Rna Splicing ◽  
Myeloproliferative Neoplasms ◽  
Chinese Patients ◽  
Newly Diagnosed ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Significant Difference ◽  
Generation Sequencing

Abstract Background Clonal hematopoiesis (CH) can be found in various myeloid neoplasms (MN), such as myelodysplastic syndromes (MDS), myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN), also in pre-MDS conditions. Methods Cytogenetics is an independent prognostic factor in MDS, and fluorescence in-situ hybridization (FISH) can be used as an adjunct to karyotype analysis. In the past 5 years, only 35 of 100 newly diagnosed MDS and MDS/MPN patients were identified abnormalities, who underwent the FISH panel. In addition, we examined a cohort of 51 cytopenic patients suspected MDS or MDS/MPN with a 20-gene next generation sequencing (NGS), including 35 newly diagnosed MN patients and 16 clonal cytopenias of undetermined significance (CCUS) patients. Results Compared with the CCUS group, the MN group had higher male ratio (22/13 vs 10/6), cytogenetics abnormalities rate (41.4% vs 21.4%) and frequency of a series of mutations, such as ASXL1 (28.6% vs 25%), U2AF1 (25.7% vs 25%), RUNX1 (20% vs 0.0%); also, higher adverse mutations proportion (75% vs 85.2%), and double or multiple mutations (54.3% vs 43.75%). There were 7 MN patients and 4 CCUS patients who experienced cardio-cerebrovascular embolism events demonstrated a significant difference between the two groups (25% vs 20%). Ten of the 11 patients had somatic mutations, half had DNA methylation, while the other half had RNA splicing. Additionally, six patients had disease transformation, and four patients had mutated U2AF1, including two CCUS cases and two MDS-EB cases. Following up to January 2021, there was no significant difference in over survival between the CCUS and MN groups. Conclusion NGS facilitates the diagnosis of unexplained cytopenias. The monitoring and management of CCUS is necessary, also cardio-cerebrovascular embolism events in patients with CH need attention in the clinical practice.

Targeted Next-Generation Sequencing for Congenital Hypothyroidism With Positive Neonatal TSH Screening

2020 ◽  
Vol 105 (8) ◽  
pp. e2825-e2833 ◽  
Author(s):  
Takeshi Yamaguchi ◽  
Akie Nakamura ◽  
Kanako Nakayama ◽  
Nozomi Hishimura ◽  
Shuntaro Morikawa ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Congenital Hypothyroidism ◽  
Gene Dosage ◽  
Next Generation ◽  
Gene Dosage Effect ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Variants ◽  
Published Evidence ◽  
Unknown Significance ◽  
Generation Sequencing

Abstract Purpose Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder; however, its molecular etiology remains poorly understood. Methods We performed genetic analysis of 24 causative genes using next-generation sequencing in 167 CH cases, comprising 57 dyshormonogenesis (DH), 32 dysgenesis (TD) and 78 undiagnosed. The pathogenicity of variants was assessed by the American College of Medical Genetics guidelines, inheritance pattern, and published evidence. Furthermore, we compared the oligogenic groups and monogenic groups to examine the correlation between variant dosage and severity. Results We identified variants in 66.5% cases (111/167) and 15 genes, DUOX2, TSHR, PAX8, TG, TPO, DUOXA2, JAG1, GLIS3, DUOX1, IYD, SLC26A4, SLC5A5, SECISBP2, DIO1, and DIO3. Biallelic variants were identified in 12.6% (21/167), oligogenic in 18.0% (30/167), and monogenic in 35.9% (60/167); however, 68.5% of variants were classified as variant of unknown significance (VUS). Further examinations showed that 3 out of 32 cases with TD (9.4%) had pathogenic variants (2 of TSHR and 1 of TPO), and 8 out of 57 cases with DH (14.0%) (7 of DUOX2, 1 of TG) had pathogenic variants. In addition, TSH levels at the first visit were significantly higher in the oligogenic group than in the monogenic group. Conclusions The detection rate of pathogenic variants in Japanese CH was similar to that previously reported. Moreover, oligogenic cases were likely to be more severe than monogenic cases, suggesting that CH may exhibit a gene dosage effect. Further analysis of VUS pathogenicity is required to clarify the molecular basis of CH.

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