Clinical and genetic analysis of a case of Gitelman syndrome with comorbid Graves disease and adrenocortical adenoma
乔彦 1赵景宏 1曹乐薇 1李云祥 2伍季 2鞠翠钰
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作者信息
1. 1南充市中心医院内分泌科，南充 637003
2. 2南充市中心医院泌尿外科，南充 637003
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摘要
目的 对1例极其罕见Gitelman综合征(GS)合并Graves病与肾上腺皮质腺瘤患者进行临床及基因变异分析。 方法 选取2020年12月21日于南充市中心医院就诊的1例GS合并Graves病与肾上腺皮质腺瘤患者为研究对象。收集该患者相关临床资料，采集患者及其家系成员的外周静脉血样，提取DNA后进行加深全外显子组测序，筛查致病基因。 结果 患者为45岁女性，因发现左侧肾上腺占位就诊，临床检查提示存在Graves病、非促肾上腺皮质激素(ACTH)依赖性Cushing综合征、低钾血症及低镁血症等，MRI提示左侧肾上腺3.8 cm×3.2 cm占位，手术病理证实为肾上腺皮质腺瘤。基因检测提示患者及其妹妹存在SLC12A3基因c.1444-10(IVS11)G>A与c.179(exon1)C>T(p.T60M)的复合杂合变异，分别遗传自其父亲和母亲。根据美国医学遗传学与基因组学学会(ACMG)相关指南，c.1444-10(IVS11)G>A与c.179(exon1)C>T(p.T60M)变异分别评级为意义不明变异(PM2_Supporting+PP3)与可能致病性(PM3_Strong+PM1+PP3)。 结论 GS合并Graves病与肾上腺皮质腺瘤暂未见相关报道，SLC12A3基因c.1444-10(IVS11)G>A变异为新发现的变异，其与c.179(exon1)C>T(p.T60M)组成的复合杂合变异可能为本研究患者的遗传学病因。 Objective To report the clinical and genetic characteristics of a rare case of Gitelman syndrome with comorbid Graves disease and ACTH-independent adrenocortical adenoma. Methods A patient who had presented at the Nanchong Central Hospital on December 21, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole-exome sequencing was carried out on DNA extracted from peripheral venous blood samples from the patient and her family members. Results The patient, a 45-year-old woman, was found to have Graves disease, ACTH-independent Cushing syndrome, hypokalemia and hypomagnesemia following the discovery of an adrenal incidentaloma. MRI scan had revealed a 3.8 cm × 3.2 cm mass in the left adrenal gland. The mass was removed by surgery and confirmed as adrenocortical adenoma. DNA sequencing revealed that the patient and her sister have both harbored compound heterozygous variants of the SLC12A3 gene, namely c. 1444-10(IVS11)G>A and c. 179(exon1)C>T (p.T60M), which were respectively inherited from their father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 1444-10(IVS11)G>A and c. 179(exon1)C>T (p.T60M) were respectively classified as a variant of uncertain significance (PM2_Supporting+ PP3) and a likely pathogenic variant (PM3_Strong+ PM1+ PP3). Conclusion The conjunction of Gitelman syndrome with Graves disease and adrenal cortex adenoma is rather rare. The newly discovered c. 1444-10(IVS11)G>A variant of theSLC12A3 gene, together with the heterozygous variant of c. 179(exon1) C>T (p.T60M), probably underlay the pathogenesis in this patient.
Abstract
Objective To report the clinical and genetic characteristics of a rare case of Gitelman syndrome with comorbid Graves disease and ACTH-independent adrenocortical adenoma. Methods A patient who had presented at the Nanchong Central Hospital on December 21, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole-exome sequencing was carried out on DNA extracted from peripheral venous blood samples from the patient and her family members. Results The patient, a 45-year-old woman, was found to have Graves disease, ACTH-independent Cushing syndrome, hypokalemia and hypomagnesemia following the discovery of an adrenal incidentaloma. MRI scan had revealed a 3.8 cm × 3.2 cm mass in the left adrenal gland. The mass was removed by surgery and confirmed as adrenocortical adenoma. DNA sequencing revealed that the patient and her sister have both harbored compound heterozygous variants of the SLC12A3 gene, namely c. 1444-10(IVS11)G>A and c. 179(exon1)C>T (p.T60M), which were respectively inherited from their father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 1444-10(IVS11)G>A and c. 179(exon1)C>T (p.T60M) were respectively classified as a variant of uncertain significance (PM2_Supporting+ PP3) and a likely pathogenic variant (PM3_Strong+ PM1+ PP3). Conclusion The conjunction of Gitelman syndrome with Graves disease and adrenal cortex adenoma is rather rare. The newly discovered c. 1444-10(IVS11)G>A variant of theSLC12A3 gene, together with the heterozygous variant of c. 179(exon1) C>T (p.T60M), probably underlay the pathogenesis in this patient.
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