Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Biomed Res Int. 2022 May 28;2022:9096999. doi: 10.1155/2022/9096999. eCollection 2022.
Hereditary coproporphyria (HCP) is a rare autosomal dominant disorder caused by a partial deficiency of coproporphyrinogen III oxidase (CPOX), and systemic lupus erythematosus (SLE) is an autoimmune disease with a strong genetic predisposition. (solute carrier family 7 member 7) may be associated with monogenic lupus disease; however, only 2 cases of concomitant HCP and SLE have been reported.
We report a 30-year-old woman with a six-year history of SLE presenting with abdominal pain, vomiting, dysuria, tachycardia, and hyponatremia. Whole exome sequencing (WES) and Sanger sequencing were carried out for the proband and members of her pedigree to detect the genetic background. The Gene Expression Omnibus (GEO) database was used to search the related gene expression profiles. Differentially expressed genes (DEGs) were identified using GEO2R.
A novel heterozygous splicing mutation of (NM_000097): c.700+2 T > C (intron 2) was detected by WES in the proband, and it was considered likely pathogenic (PSV1+PM2). Sanger sequencing verified the heterozygous mutation of in the proband, although it was not detected in her father. WES also identified 62 other gene variants, especially two heterozygous variants in (NM_001126106): c.250G > A (p. V84I) and c.625+1G > A (splicing). DEGs were detected from GSE51997, and the expression of was downregulated in SLE patients compared with normal controls (adj. = 0.0071, logFC = -1.0975).
This study presents the first reported case of SLE coexisting with HCP in China; moreover, a novel splicing mutation of , i.e., c.700+2 T > C (intron 2), and two heterozygous mutations of were reported. The simultaneous mutations of and may explain the etiopathogenetic connections of HCP and SLE.
遗传性粪卟啉症（HCP）是一种由粪卟啉原氧化酶（CPOX）部分缺乏引起的罕见常染色体显性遗传疾病，而系统性红斑狼疮（SLE）是一种具有强烈遗传倾向的自身免疫性疾病。溶质载体家族 7 成员 7（SLC7A7）可能与单基因狼疮病有关；然而，仅报告了 2 例同时存在 HCP 和 SLE 的病例。
我们报告了一例 30 岁女性，患有 SLE6 年，表现为腹痛、呕吐、尿痛、心动过速和低钠血症。对先证者及其家族成员进行全外显子组测序（WES）和 Sanger 测序，以检测遗传背景。使用基因表达综合数据库（GEO）搜索相关基因表达谱。使用 GEO2R 识别差异表达基因（DEGs）。
通过 WES 在先证者中检测到 SLC7A7 的一个新的杂合剪接突变（NM_000097）：c.700+2T>C（内含子 2），被认为可能具有致病性（PSV1+PM2）。Sanger 测序证实了先证者中 SLC7A7 的杂合突变，但在其父亲中未检测到。WES 还鉴定了 62 个其他基因变异，特别是 SLC7A7 的两个杂合变异（NM_001126106）：c.250G>A（p.V84I）和 c.625+1G>A（剪接）。从 GSE51997 中检测到 DEGs，与正常对照相比，SLE 患者中 SLC7A7 的表达下调（adj. = 0.0071，logFC = -1.0975）。
本研究报道了首例中国 SLE 合并 HCP 的病例；此外，还报道了 SLC7A7 的一个新的剪接突变，即 c.700+2T>C（内含子 2），以及 SLC7A7 的两个杂合突变。SLC7A7 和 SLC7A7 的同时突变可能解释了 HCP 和 SLE 的病因发病机制联系。
