Single-gene (monogenic) etiologies are common in childhood-onset lupus, according to study results published in Pediatric Rheumatology.

These results emphasize the need for early and accurate etiology-based diagnoses in children with severe or atypical lupus to improve clinical management.

The study included 15 patients (age range, 2-18 years) with childhood-onset lupus from January 2015 to June 2018.  A total of 6 patients with severe and/or atypical presentations were identified for genomic sequencing and 4 of them were diagnosed with monogenic lupus.

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The researchers used whole exome sequencing (WES) to identify the cases that were explained by a monogenic cause. They mapped sequence reads to the human reference genome assembly using CLC Genomics Workbench software.

Using WES, the researchers identified causative mutations in 4 patients in 5 different genes: C1QC, SLC7A7, MAN2B1, PTEN, and STAT1. In a patient with a mutation in the gene C1QC, the researchers identified a novel homozygous truncating mutation that resulted in a premature stop codon. In another patient, the researchers identified 2 homozygous mutations in MAN2B1 and SLC7A7 causing alpha-mannosidosis and lysinuric protein intolerance, respectively.

A PTEN mutation presented as severe lupus with macrocephaly, development delay, pigmented gums, and pigmented macules of the glans penis. In a patient with STAT mutations, the symptoms presented as chronic mucocutaneous candidiasis with autoimmunity.

Before undergoing genetic testing, no molecular diagnoses had been established on clinical findings.

“An unbiased genetic screening of larger cohorts of patients with childhood-onset SLE with diverse clinical presentations is needed to better estimate the prevalence of monogenic etiology for pediatric SLE,” the researchers wrote.

Reference

Tirosh I, Spielman S, Barel O, et al. Whole exome sequencing in childhood-onset lupus frequently detects single gene etiologies. Pediatric Rheumatol. 2019;17:52.