Systemic Lupus Erythematosus and Hereditary Coproporphyria: Two Different Entities Diagnosed by WES in the Same Patient.

BACKGROUND

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.

METHODS

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.

RESULT

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).

CONCLUSION

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.