Molecular Analysis of Congenital Hypothyroidism in Saudi Arabia: SLC26A7 Mutation Is a Novel Defect in Thyroid Dyshormonogenesis

Zou, Minjing; Alzahrani, Ali S.; Al‐Odaib, Ali; Alqahtani, Mohammad A.; Babiker, Omer; Al-Rijjal, Roua A.; BinEssa, Huda A.; Kattan, Walaa E; Al-Enezi, Anwar F; Qarni, Ali Al; Al-Faham, Manar S A; Baitei, Essa Y.; Alsagheir, Afaf; Meyer, Brian F.; Shi, Yufei

doi:10.1210/jc.2017-02202

Cited by 55 publications

(50 citation statements)

References 52 publications

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“…We found almost 70% mutations related to thyroid dyshormonogenesis in our cohort, and most of mutations were present as heterozygous, which was different from the reports in other regions [39]. We classified the type of mutant CH patients according to the pathomechanism of the genes, 57.97% CH patients were classified as thyroid dyshormonogenesis.…”

Section: Discussioncontrasting

confidence: 92%

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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Section: Discussioncontrasting

confidence: 92%

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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“…The most frequent genetic defects in thyroid dyshormonogenesis and dysgenesis were TG and TSHR mutations, respectively. The proportion of patients with TSHR mutations was 10.9% [48], which was significantly higher than that previously reported in Chinese patients (1.6%) [55]. Furthermore, TSHR mutations in Saudi patients were biallelic, whereas all TSHR mutations in Chinese patients were monoallelic, which may not cause symptomatic CH [55].…”

Section: Congenital Hypothyroidismcontrasting

confidence: 55%

“…The main cause of CH is insufficient production of thyroid hormone in newborns, which can lead to failure to grow and mental retardation [48]. CH is classified into two types: (1) thyroid dysgenesis, in which defective thyroid gland development leads to athyreosis, thyroid ectopy and hypoplasia [49], and (2) thyroid dyshormonogenesis, which is a defect in thyroid hormone synthesis [50].…”

Section: Congenital Hypothyroidismmentioning

confidence: 99%

Diagnosis and Management of Hypothyroidism in Gulf Cooperation Council (GCC) Countries

et al. 2020

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Hypothyroidism is one of the most common chronic endocrine conditions. However, as symptoms of hypothyroidism are non-specific, up to 60% of those with thyroid dysfunction are unaware of their condition. Left untreated, hypothyroidism may contribute to other chronic health conditions. In the Arabian Gulf States, hypothyroidism is thought to be common, but is underdiagnosed, and management approaches vary. An advisory board of leading Saudi endocrinologists and policy advisers was convened to discuss and formulate recommendations for the diagnosis and management of hypothyroidism in Saudi Arabia based on their clinical expertise. The final document was shared with leading endocrinologists from the other Gulf Cooperation Council (GCC) and aconsensus report was generated and summerized in this article. While there is no consensus Digital Features To view digital features for this article go to

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“…A greater reduction of T4 than T3, together with a partial iodide organification defect in humans with homozygous SLC26A7 defects is consistent with reduced TG iodination leading to dyshormonogenesis. Indeed, since the first submission of this report, biallelic, truncating mutations in SLC26A7 were reported in a single Saudi Arabian family with dyshormonogenetic CH (8). Due to differing dietary iodine intake, variable TSH levels in utero, genetic background, and other unknown factors, variability of goiter (presence and size) is recognized in dyshormonogenesis despite identical genetic basis (9).…”

Section: Discussionmentioning

confidence: 92%

Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism

Cangül¹,

Liao²,

Schoenmakers³

et al. 2018

JCI Insight

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Molecular Analysis of Congenital Hypothyroidism in Saudi Arabia: SLC26A7 Mutation Is a Novel Defect in Thyroid Dyshormonogenesis

Abstract: TG and TSHR mutations are the most common genetic defects in Saudi patients with CH. The prevalence of other disease-causing mutations is low, reflecting the consanguineous nature of the population. SLC26A7 mutations appear to be associated with thyroid dyshormonogenesis.

Cited by 55 publications

References 52 publications

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

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

Diagnosis and Management of Hypothyroidism in Gulf Cooperation Council (GCC) Countries

Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism

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