A Case Report of SYNE1 Deficiency-Mimicking Mitochondrial Disease and the Value of Pangenomic Investigations.

Mitochondrial disorders are characterized by a huge clinical, biochemical, and genetic heterogeneity, which poses significant diagnostic challenges. Several studies report that more than 50% of patients with suspected mitochondrial disease could have a non-mitochondrial disorder. Thus, only the identification of the causative pathogenic variant can confirm the diagnosis. Herein, we describe the diagnostic journey of a family suspected of having a mitochondrial disorder who were referred to our Genetics Department. The proband presented with the association of cerebellar ataxia, COX-negative fibers on muscle histology, and mtDNA deletions. Whole exome sequencing (WES), supplemented by a high-resolution array, comparative genomic hybridization (array-CGH), allowed us to identify two pathogenic variants in the non-mitochondrial SYNE1 gene. The proband and her affected sister were found to be compound heterozygous for a known nonsense variant (c.13258C>T, p.(Arg4420Ter)), and a large intragenic deletion that was predicted to result in a loss of function. To our knowledge, this is the first report of a large intragenic deletion of SYNE1 in patients with cerebellar ataxia (ARCA1). This report highlights the interest in a pangenomic approach to identify the genetic basis in heterogeneous neuromuscular patients with the possible cause of mitochondrial disease. Moreover, even rare copy number variations should be considered in patients with a phenotype suggestive of SYNE1 deficiency.

The association of urinary plasmin level with renal involvement and disease flare among systemic lupus erythematosus patients.

Objectives: To explore the ability to use urinary level of plasmin as an indicator for renal affection and activity in systemic lupus erythematosus (SLE) patients. Patients and methods: Between April 2020 and October 2020, urine samples from 50 SLE patients (2 males, 48 females; mean age: 35.5±8.1 years; range, 22 to 39 years) and 20 age- and sex-matched healthy controls (2 males, 18 females; mean age: 34.1±6.5 years; range, 27 to 38 years) were collected. The patients were divided into two groups according to the presence or absence of renal manifestations as those with renal disease (n=28) and those without renal disease (n=22). The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), renal activity (rSLEDAI), and Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) scores were calculated. Renal biopsy was performed to patients with active lupus nephritis (LN). The activity index (AI) and Chronicity Index (CI) were scored. Results: There was a highly statistically significant difference in the mean urinary plasmin levels between SLE cases and the control group (88.9±42.6 ng/mL vs. 21.3±26.8 ng/mL, respectively; p<0.001). A significant elevation was observed (p<0.05) in patients with LN (97.9±46.6 ng/mL) than without (42.7±12.7 ng/mL), particularly in patients with active renal involvement (82.9±26.6 ng/mL) than patients with inactive renal disease (63.2±15.5 ng/mL). There were significant positive correlations between the mean urinary plasmin levels and inflammatory markers, SLEDAI, and rSLEDAI scores. Conclusion: Urinary level of plasmin is significantly elevated among SLE cases, particularly in those with active LN. The remarkable association between urinary plasmin level and various activity status implies that urinary plasmin can be used as a beneficial marker to monitor lupus nephritis flare.