Department of Pediatrics, Pusan National University School of Medicine, Busan, Korea.
Green Cross Genome, Pusan National University Hospital, Busan, Korea.
Ann Clin Lab Sci. 2021 Jan;51(1):73-81.
To analyze the genetic causes of congenital hypothyroidism through the targeted exome sequencing of pediatric patients with congenital hypothyroidism with thyroid gland METHOD: The study population included 20 patients diagnosed with congenital hypothyroidism with thyroid gland at the Pediatric Endocrinology Clinic of Pusan National University Hospital. Targeted exome sequencing was performed on eight causative genes, including thyroid stimulating hormone receptor (), mutation in which can cause hypothyroidism with a small or normal sized thyroid gland, and thyroglobulin (), thyroid peroxidase (), dual oxidase 2 (), dual oxidase maturation factor 2 (), iodotyrosine deiodinase (), solute carrier family 26 member 4 (SLC26A4), and solute carrier family 5 member 5 (), mutations in which are known to cause thyroid dyshormonogenesis.
Permanent, subclinical, and transient hypothyroidism were diagnosed in 15 (75%), three (15%), and two (10%) patients, respectively. Genetic mutations were identified in 16 patients (80% positivity rate). Targeted exome sequencing of eight genes identified 24 variants in these patients: 11 variants in eight patients; six variants in five patients; five variants in three patients; and two variants in two patients. Of these 24 variants, 10 (41.6%) were novel. No variants were identified in , or . Two patients displayed triallelic (digenic) mutations (in and in one patient and and in the other). No variants were identified in three patients with permanent hypothyroidism and one patient with transient hypothyroidism. Genetic variations that could explain the congenital hypothyroidism phenotypes were identified in 12/15 cases (80%).
Targeted exome sequencing identified the genetic causes of congenital hypothyroidism with thyroid gland in 80% of the patients studied, with and mutations being the most common. As many of the identified variants were novel, additional studies on the genetic causes of congenital hypothyroidism are warranted.
通过对甲状腺发育正常的先天性甲状腺功能减退症患儿进行靶向外显子组测序，分析其遗传病因。
研究人群包括 20 名在釜山大学医院儿科内分泌科被诊断为甲状腺发育正常的先天性甲状腺功能减退症患儿。对 8 个致病基因（包括促甲状腺激素受体 ()、突变可导致甲状腺体积小或正常的甲状腺功能减退症，甲状腺球蛋白 ()、甲状腺过氧化物酶 ()、双氧化酶 2 ()、双氧化酶成熟因子 2 ()、碘酪氨酸脱碘酶 ()、溶质载体家族 26 成员 4 ()和溶质载体家族 5 成员 5 ()，突变可导致甲状腺激素合成障碍）进行靶向外显子组测序。
15 名（75%）患者被诊断为永久性、亚临床和暂时性甲状腺功能减退症，2 名（10%）患者被诊断为暂时性甲状腺功能减退症。16 名患者（80%阳性率）发现基因突变。对 8 个基因进行靶向外显子组测序，在这些患者中发现了 24 个变异：8 名患者中有 11 个变异；5 名患者中有 6 个变异；3 名患者中有 5 个变异；2 名患者中有 2 个变异。其中 10 个（41.6%）变异是新的。未在 或 中发现变异。两名患者显示三等位基因（双等位基因）突变（一名患者中为 和 ，另一名患者中为 和 ）。3 名永久性甲状腺功能减退症患者和 1 名暂时性甲状腺功能减退症患者未发现变异。在 15 例（80%）先天性甲状腺功能减退症患者中发现了可解释其表型的遗传变异。
靶向外显子组测序确定了 80%研究患者甲状腺发育正常的先天性甲状腺功能减退症的遗传病因，最常见的是 和 突变。由于许多鉴定的变异是新的，因此需要进一步研究先天性甲状腺功能减退症的遗传病因。
