Exome sequencing identifies SLC26A4, GJB2, SCARB2 and DUOX2 mutations in 2 siblings with Pendred syndrome in a Malaysian family

Chow, Yock-Ping; Murad, Nor Azian Abdul; Rani, Zamzureena Mohd; Khoo, Jia-Shiun; Chong, Pei-Sin; Wu, Loo-Ling; Jamal, Rahman

doi:10.1186/s13023-017-0575-7

Cited by 9 publications

(6 citation statements)

References 51 publications

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“…The variants p.K530X (7%), p.L1343F (6%) and p.R1110Q (4.7%) were highly recurrent in our cohort. Among these three variants c.1588A>T (p.K530X) had a highest rate in our study and the result is in accordance with the previous studies in Asians including Chinese, Japanese, Korean and Malaysian 12,14,17,18 . Of all pathogenic variants predicted by ACMG/AMP, the variants p.R1110Q, p.R885L and p.1160del have been identified to be the important causes of CH.…”

Section: Discussionsupporting

confidence: 92%

Mutation Screening of DUOX2 Gene in Children with Congenital Hypothyroidism

Chen¹,

Liu²,

Liu³

et al. 2020

Preprint

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Background: Congenital hypothyroidism(CH) is generally known as the most common neonatal endocrine disorder. However, the mutational spectrum of DUOX2 gene and the relationship between genotype and phenotype have not been fully established among Chinese CH patients. Therefore, The aim of this study was to screen DUOX2 mutations in Chinese patients with CH and to research the relationship between DUOX2 genotype and clinical phenotype.Methods: Eighty-six patients with CH were recruited from northeastern region of China. Peripheral venous blood samples were collected, genomic DNA was extracted , PCR and next-generation sequencing (NGS) were used to analyze all exons of DUOX2. Detailed medical data were collected, and the relationship between DUOX2 genotype and the clinical phenotype was preliminarily investigated.Results: NGS analysis of DUOX2 gene identified a total of 20 different gene variants in 26 patients(30.2%), which was consistent with the gene variants in Asian populations, among these variants 16 were known to be pathogenic or likely to be pathogenic, and four were suspected to be of uncertain significance. Three mutations (p.K530X, p.L1343F and p.R1110Q) were highly recurrent in our patient cohort. By using protein homology modeling method, the analysis of its three-dimensional structure suggested that the mutations p.336_337del and p.T1107fs caused the change of the protein.Conclusions: In our study, p.336_337del and p.T1107fs were found to be novel variants and p.K530X with the highest prevalence. Children with DUOX2 single allele heterozygous mutation or compound heterozygous mutation exhibited different morphological developments of the thyroid.

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Section: Discussionsupporting

confidence: 92%

Mutation Screening of DUOX2 Gene in Children with Congenital Hypothyroidism

Chen¹,

Liu²,

Liu³

et al. 2020

Preprint

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“…The c.1588A > T mutation in DUOX2 , which is responsible for thyroid dyshormonogenesis, was highly recurrent, with a prevalence of 1/40,000. The c.1588A > T mutation is population specific and has been reported mainly in Asian populations, including Chinese ( Fu et al, 2015 , 2016a ; Tan et al, 2016 ), Japanese ( Maruo et al, 2008 , 2016 ), and Malaysian ( Chow et al, 2017 ) populations. The c.4027C > T ( Chen et al, 2018 ), c.3329G > A ( Fu et al, 2015 ; Park et al, 2016 ), c.3632G > A ( Chai et al, 2015 ), c.2335G > A ( Jiang et al, 2016 ; Maruo et al, 2016 ), and c.2654G > A ( Zheng et al, 2016 ) mutations are also predominant in Asians, mostly in the Chinese Han population c.1883delA ( Maruo et al, 2008 , 2016 ; Park et al, 2016 ; Tan et al, 2016 ), c.3478_3480del ( Narumi et al, 2011 ; Fu et al, 2016a ; Park et al, 2016 ), and c.605_621del ( Jin et al, 2014 ; Matsuo et al, 2016 ; Tan et al, 2016 ) show a scattered distribution in Asian populations, including China, Japan, and South Korea.…”

Section: Discussionmentioning

confidence: 99%

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

Long

Yang

et al. 2018

Front. Genet.

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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.

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“…The mutation of c.1588A>T in DUOX2 was highly recurrent with an approximately prevalence of 1/40,000 in our cohort, which was responsible for thyroid dyshormonogenesis. c.1588A>T had population-specificity and mainly reported in Asia population, including China [7][8][9], Japan [10,11] and Malaysia [12]. Mutations of c.4027C>T [13], c.3329G>A [7,14], c.3632G>A [15], c.2335G>A [11,16] and c.2654G>A [17] were also mainly reported in Asians, and most of them were identified in Chinese Han [9][10][11]14], c.3478_3480del [8,14,18] and c.605_621del [9,19,20] were scattered distribution in Asia, including China, Japan and Korea.…”

Section: Discussionmentioning

confidence: 99%

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

Long

Zhou

et al. 2018

Endocr J

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To identify the spectrum and prevalence of thirteen causative genes mutations in congenital hypothyroidism (CH) patients, we collected blood samples and extracted genomic DNA of 106 CH patients, and designed a customized targeted next-generation sequencing panel containing 13 CH-causing genes to detect mutations. A total of 132 mutations were identified in 65.09% of patients (69/106) on the following nine genes: DUOX2, TG, TPO, TSHR, TTF1, TTF2, NKX2-5, PAX8 and GNAS. 69.70% (92/132) mutations related to thyroid dyshormonogenesis genes, including DUOX2 (n = 49), TG (n = 35), and TPO (n = 8). 21.21% (28/132) mutations related to thyroid dysgenesis genes, including TSHR (n = 19), TTF1 (n = 5), TTF2 (n = 1), PAX8 (n = 2), and NKX2-5 (n = 1). 9.09% (12/132) mutations related to GNAS, which was associated with thyrotropin resistance. No mutation of THRA, TSHB, IYD or SLC5A5 was detected. Among 69 mutations detected patients, 41 (59.42%) patients were two or more mutations detected, and mutations of 30 (43.48%) patients related to two or three genes. According to the pathomechanism of the mutant genes, 57.97% CH patients were classified as thyroid dyshormonogenesis. Overall, DUOX2, TG and TSHR mutations were the most common genetic defects in Chinese CH patients, and thyroid dyshormonogenesis could be the first genetic etiology of CH in Chinese. Besides, multiple mutations accounts for a part of genetic pathogenesis.

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Exome sequencing identifies SLC26A4, GJB2, SCARB2 and DUOX2 mutations in 2 siblings with Pendred syndrome in a Malaysian family

Cited by 9 publications

References 51 publications

Mutation Screening of DUOX2 Gene in Children with Congenital Hypothyroidism

Mutation Screening of DUOX2 Gene in Children with Congenital Hypothyroidism

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

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

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