A novel c.1391_1428delinsT mutation in TSHR as a cause of familial congenital hypothyroidism with delayed onset

Watanabe, Daisuke; Yagasaki, Hideaki; Ishii, Shuji; Mitsui, Yumiko; Nakane, Takaya; Inukai, Takeshi

doi:10.1016/j.pedneo.2019.11.003

Cited by 4 publications

(2 citation statements)

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“…NGS identified a total of 24 variants in 14 patients after removing unselected variants. As shown in Table 3, the variants were distributed in 15 sites (six novel sites and nine previously reported sites) of five genes [6,[20][21][22][23][24][25][26]. Eight, five, eight, two, and one variants were found to be potentially pathogenic in DUOX2, TSHR, TG, UBR1, and TPO genes, respectively.…”

Section: Resultsmentioning

confidence: 87%

Screening of frequent variants associated with congenital hypothyroidism: a comparison with next generation sequencing

et al. 2021

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Congenital hypothyroidism (CH) is considered the most common congenital endocrine disorder of genetic origin. Next generation sequencing (NGS) is the standard method for identifying genetic mutations, but it is an expensive and complex technique. Therefore, we propose to use Sanger sequencing to identify selected variants of the four most common CH-causative genes: DUOX2, TG, TSHR, and PAX8. To analyze the performance of Sanger sequencing, we compared its variant detection ability with that of a CH NGS panel containing 53 genes. We performed Sanger sequencing of selected variants and panel NGS analysis of 25 Japanese patients with CH. Sanger sequencing identified nine variants in seven patients, while NGS identified 24 variants in 14 patients. Of these, eight, five, eight, two, and one were found to be potentially pathogenic in DUOX2, TSHR, TG, UBR1, and TPO genes, respectively. The percentage of detectable variants using Sanger sequencing compared with NGS was 37.5% (9/24 variants), whereas the percentage of detectable cases carrying variants using Sanger sequencing compared with NGS was 50% (7/14 patients). We proposed a system for screening commonly identified CH-related variants by Sanger sequencing. Sanger sequencing could therefore identify about a third of CH-causative variants, so is considered an effective and efficient form of pre-screening before NGS.

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Section: Resultsmentioning

confidence: 87%

Screening of frequent variants associated with congenital hypothyroidism: a comparison with next generation sequencing

et al. 2021

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“…To date, numerous studies have reported genetic causes in CH patients, and several lines of evidence support a relevant genetic origin for CH. [2][3][4][5] According to the causes of the underlying mutated genes, the genetic classification divides CH into two main categories, thyroid dysgenesis and thyroid dyshormonogenesis. The defects of thyroid dysgenesis are classified as agenesis (complete lack of thyroid tissue), ectopy (located in an improper position), hemiagenesis or hypoplasia (severely reduced thyroid size).…”

Section: Introductionmentioning

confidence: 99%

Variant of TSHR is Not a Frequent Cause of Congenital Hypothyroidism in Chinese Han Patients

Xue

Yang

et al. 2021

IJGM

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Purpose To screen variants of the thyroid stimulating hormone receptor ( TSHR ) gene among congenital hypothyroidism (CH) patients. Patients and Methods We conducted a genetic screening of the TSHR gene in a cohort of 125 Chinese CH patients. Variants were detected by customized targeted next-generation sequencing. Results A total of 11 TSHR missense heterozygous variants were identified in 14 CH patients. Six variants were in the transmembrane domains, four variants were in the leucine-rich repeats and one variant was located in the hinge region of the TSHR protein. p.F525S was the most prevalent variant with an allele frequency of 0.016, followed by p.R450H with an allele frequency of 0.012. The allele frequency of most variants was higher in our cohort than those of other populations. Conclusion The prevalence of TSHR variants was 11.2%. Variant p.F525S was the most prevalent variant with an allele frequency of 0.016. The prevalence of TSHR variants was different from other populations.

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Congenital Hypothyroidism Patients With Thyroid Hormone Receptor Variants Are Not Rare: A Systematic Review

Wang

et al. 2021

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Background Primary congenital hypothyroidism (CH) is a common endocrine and metabolic disease. Various genetic factors, including the thyroid hormone receptor (TSHR), play an important role in CH. Aim To explore the occurrence of pathogenic TSHR variants in CH. Methods We searched published articles in PubMed, Web of Science, and Cochrane Library databases, from the establishment of the database to September 26, 2021. Studies with sequencing partial or full exons of TSHR in CH patients were included. Gene polymorphism was excluded. Results A total of 66 articles (44 case-control studies and 22 case reports) were selected from the database. Though case-control studies, we found the incidence of pathogenic TSHR variants were not rare (range from 0% to 30.6%) and varied greatly in different countries and race. The pathogenic genotypes varied in different regions. All the variants were “loss-of-function” mutations, in which the p.(Arg450His) variant was the most common variant. In addition, we analyzed the case reports and found that CH patients with a family genetic background expressed homozygous genotypes. Homozygotes had more obvious symptoms of hypothyroidism and higher risk of comorbidities than heterozygotes. Conclusion Pathogenic TSHR variants are not uncommon cause of the CH, especially in the Arabs. The role of TSHR gene detection in the treatment of children with CH needs to be further studied.

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A novel c.1391_1428delinsT mutation in TSHR as a cause of familial congenital hypothyroidism with delayed onset

Cited by 4 publications

References 6 publications

Screening of frequent variants associated with congenital hypothyroidism: a comparison with next generation sequencing

Screening of frequent variants associated with congenital hypothyroidism: a comparison with next generation sequencing

Variant of TSHR is Not a Frequent Cause of Congenital Hypothyroidism in Chinese Han Patients

Congenital Hypothyroidism Patients With Thyroid Hormone Receptor Variants Are Not Rare: A Systematic Review

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