Clinical and genetic investigation in patients with permanent congenital hypothyroidism
Clinical and genetic investigation in patients with permanent congenital hypothyroidism
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永久性先天性甲状腺功能减退症患者的临床和遗传学调查
DOI：
10.1016/j.cca.2022.11.007
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发表时间：
2022
影响因子：
5
通讯作者：
Bin Yu
中科院分区：
文献类型：
--
作者：
Lingna Zhou;Shuang Liu;Wei Long;Lei-lei Wang;Bin Yu
永久性先天性甲状腺功能减退症（CH）通常是一种更严重的CH类型。然而，永久性CH的分子病因和临床特征尚不清楚。方法对42例确诊为CH的患者进行随访。记录诊断和治疗时的人口统计信息和数据。采用全外显子组测序进行遗传分析。根据是否存在变异和临床特征的差异，我们对研究参与者进行分组并分析他们的特征。结果共有29例（69.0%）患者被鉴定为具有可能与其疾病相关的变异。在24例正常大小甲状腺原位（GIS）或甲状腺肿患者中，23例（95.8%,P < 0.001）存在变异。这与18例甲状腺发育不良（TD）患者进行了比较，其中6例（33.3%）有遗传变异。我们在6个基因中检测到55个变异，最常见的突变基因是duox2（70.9%）。24例GIS或甲状腺肿患者中有14例（58.3%）检测到双等位基因duox2变异。与变异病例相比，2岁和3岁时的L-T4剂量和当前剂量在未突变病例中较高。在2岁时，TD患者需要更高剂量的L-T4补充。患有duox2变异的患者在2岁和3岁以及现在需要较低剂量的L-T4。此外，患有GIS或甲状腺肿大的duox2变异患者的L-T4剂量较低。结论CH患者，无论是TD、GIS还是甲状腺肿，都有发展为永久性疾病的风险。与TD患者相比，GIS或甲状腺肿患者的变异检出率更高。最常见的突变基因是双等位基因duox2。随着年龄的增长，TD患者需要更高剂量的L-T4补充，而duox2变体患者需要相对较低的剂量。
BackgroundPermanent congenital hypothyroidism (CH) is usually a more severe type of CH. However, the molecular etiology and clinical features of permanent CH remain unclear.MethodsWe recruited 42 patients who were diagnosed with CH and followed-up after diagnosis. Demographic information and data at diagnosis and treatment were recorded. Genetic analyses were performed using whole exome sequencing. Based on the presence or absence of variants and differences in clinical features, we grouped the study participants and analyzed their characteristics.ResultsA total of 29 patients (69.0 %) were identified as having variants potentially related to their disease. Among the 24 patients with normal-sized thyroid gland-in-situ (GIS) or goiter, 23 (95.8 %, P < 0.001) had variants. This is compared to 18 patients with thyroid dysgenesis (TD), of which six (33.3 %) had genetic variants. We detected 55 variants in six genes, the most frequently mutated gene beingDUOX2(70.9 %). BiallelicDUOX2variants were detected in 14 of 24 (58.3 %) GIS or goiter patients. Compared to the cases with variants, the L-T4 dose at 2 and 3 years of age and current dose were higher in the unmutated cases. At 2 years of age, patients with TD required higher doses of L-T4 supplementation. Patients withDUOX2variants showed lower doses of L-T4 being required at 2 and 3 years of age and current. Furthermore, patients with GIS or goiter withDUOX2variants showed lower doses of L-T4.ConclusionsPatients with CH, whether TD or GIS or goiter, are at risk of developing a permanent condition. Compared with patients with TD, the detection of variants was higher in patients with GIS or goiter. The most frequently mutated gene wasDUOX2,with a biallelic type. Patients with TD required higher doses of L-T4 supplementation with age, whereas those patients with theDUOX2variant required relatively lower doses.