妊娠合并罗托综合征1例报告

高立洁; 莫艳波; 梁笑楠; 张晓岚

doi:10.12449/JCH260321

妊娠合并罗托综合征1例报告

DOI: 10.12449/JCH260321

1.
河北医科大学第二医院消化内科，石家庄 050035
2.
华北理工大学附属医院消化内科，河北唐山 063000

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：高立洁负责课题设计，资料收集和分析，撰写及修改论文；莫艳波负责资料收集和修改论文；梁笑楠负责修改论文；张晓岚负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
张晓岚， xiaolanzh@126.com （ORCID： 0009-0001-5091-2812）

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出版历程
- 收稿日期: 2025-07-02
- 录用日期: 2025-08-25
- 出版日期: 2026-03-25

Rotor syndrome in pregnancy： A case report

1.
Department of Gastroenterology，The Second Hospital of Hebei Medical University，Shijiazhuang 050035，China
2.
Department of Gastroenterology，The Affiliated Hospital of North China University of Science and Technology，Tangshan，Hebei 063000，China

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Corresponding author: ZHANG Xiaolan， xiaolanzh@126.com （ORCID： 0009-0001-5091-2812）

摘要

摘要: 罗托综合征是一种常染色体隐性胆红素代谢障碍性疾病，因其极为罕见且临床表现缺乏特异性，难以诊断和鉴别。近年来，基因检测技术的发展为不典型患者的早期诊断提供了可能。经检索，目前仅有19例详尽临床及遗传数据的病例被报道。本文报道了1例妊娠期间以直接胆红素水平升高为主、溶质载体有机阴离子转运蛋白家族成员1B1/1B3双基因纯合突变诊断为罗托综合征并成功分娩的孕妇，并对相关文献进行回顾性分析，旨在从遗传机制角度探讨罗托综合征的早期精准诊断与用药策略。
- Rotor综合征 /
- 妊娠 /
- 诊断
Abstract: Rotor syndrome is an autosomal recessive disorder of bilirubin metabolism， and it is difficult to diagnose and differentiate due to its extreme rarity and a lack of specific clinical manifestations. In recent years， the development of genetic testing technology has enabled the early diagnosis of atypical patients. Literature search shows that only 19 cases with detailed clinical and genetic data have been reported. This article reports a case of a pregnant woman with an increase in direct bilirubin during pregnancy who was diagnosed with Rotor syndrome based on a bi-allelic mutation in the SLCO1B1 and SLCO1B3 genes and delivered successfully at last， and a retrospective analysis was performed for related articles， in order to facilitate the early accurate diagnosis of patients with Rotor syndrome and guide medications from the perspective of genetic mechanisms.
- Rotor Syndrome /
- Pregnancy /
- Diagnosis

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注：验证位点为SLCO1B1 NM_006446.5：exon13：c.1738C>T：p.R580*，染色体位置为chr12：21375289C>T。红色箭头为突变位点。

图 1 桑格测序结果

Figure 1. Sanger sequencing results

下载: 全尺寸图片幻灯片

注： SLCO1B3基因5号内含子区域大片段插入突变L1 insertion；染色体位置chr12：21014093-21014094。SLCO1B3，溶质载体有机阴离子转运蛋白家族成员1B3基因。

图 2 聚合酶链反应产物琼脂糖凝胶电泳结果

Figure 2. Results of agarose gel electrophoresis of PCR products

下载: 全尺寸图片幻灯片

表 1 患者历次胆红素数据

Table 1. Patient’s historical bilirubin data

次数	妊娠	日期	TBil（μmol/L）	DBil（μmol/L）	IBil（μmol/L）	DBil/TBil（%）
1	无	2021/09/10	95.01	41.10	53.91	43.26
2	无	2021/12/02	101.90	46.40	55.50	45.53
3	无	2022/07/11	74.70	31.90	42.80	42.70
4	无	2023/07/15	90.40	40.30	50.10	44.58
5	孕30周+5天	2024/10/23	120.13	61.64	58.49	51.31
6	孕38周+5天	2024/12/18	127.88	69.23	58.65	54.14
7	产后0周+4天	2024/12/25	119.25	67.36	51.89	56.93
8	产后6周+4天	2025/02/06	125.67	65.53	60.14	52.14
注：TBil，总胆红素；DBil，直接胆红素；IBil，间接胆红素。

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表 2 新生儿TcB测定结果

Table 2. Results of neonatal transcutaneous bilirubin measurements

时间（h）	TcB（mg/dL）	时间（h）	TcB（mg/dL）
24×0+0	1.2	24×3+0	12.0
24×0+6	5.4	24×3+6	11.9
24×0+12	6.5	24×3+12	12.1
24×0+18	6.1	24×3+18	12.0
24×1+0	8.5	24×4+0	11.8
24×1+6	9.0	24×4+6	11.6
24×1+12	10.6	24×4+12	11.9
24×1+18	9.8	24×4+18	12.4
24×2+0	9.1	24×5+0	11.3
24×2+6	10.3	25×5+6	11.5
24×2+12	11.0	25×5+12	11.2
24×2+18	10.8	24×5+18	—
注：TcB，经皮胆红素。

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表 3 与受检者临床信息相关的致病变异或可疑变异

Table 3. Pathogenic or suspected variants associated with clinical information about the subject

基因（组）	染色体位置hg19	变异命名	人群频率	合子状态	ACMG分类	关联疾病
SLCO1B3	chr12：21014093- 21014094	NM_019844 intron5 insLINE-1	—	纯合	致病	罗托型高胆红素血症（237450， DR）
SLCO1B1	chr12：21375289 C>T	NM_006446.5 exon13 c.1738C>T p.R580^*	0.004 241 67	纯合	致病	罗托型高胆红素血症（237450， DR）
UGT1A1	chr2：234669144 G>A	NM_000463.3 exon1 c.211G>A p.G71R	0.153 8	杂合	疾病相关多态位点	家族性暂时新生儿高胆红素血症（237900，AD，AR）、克里格勒- 纳贾尔综合征Ⅰ型（218800， AR）、克里格勒-纳贾尔综合征Ⅱ 型（606785，AR）、吉尔伯特综合征（143500，AR）
NPC2	chr14：74947448 T>C	NM_006432.5 exon4 c.398A>G p.D133G	—	杂合	意义不明确	尼曼-匹克病C2型（607625，AR）
注：ACMG，美国医学遗传学与基因组学学会；SLCO1B3，溶质载体有机阴离子转运蛋白家族成员1B3基因；SLCO1B1，溶质载体有机阴离子转运蛋白家族成员1B1基因；UGT1A1，尿苷二磷酸葡萄糖醛酸转移酶1A1基因；NPC2，尼曼-匹克病C型细胞内胆固醇转运蛋白2基因；DR，双基因隐性遗传；AD，常染色体显性遗传；AR，常染色体隐性遗传。

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