Identification of RP1 as the genetic cause of retinitis pigmentosa in a multi-generational pedigree using Extremely Low-Coverage Whole Genome Sequencing (XLC-WGS).

MOTIVATION: Next-generation sequencing (NGS) technologies are decisive for discovering disease-causing variants, although their cost limits their utility in a clinical setting. A cost-mitigating alternative is an extremely low coverage whole-genome sequencing (XLC-WGS). We investigated its use to identify causal variants within a multi-generational pedigree of individuals with retinitis pigmentosa (RP). Causing progressive vision loss, RP is a group of genetically heterogeneous eye disorders with approximately 60 known causal genes. RESULTS: We performed XLC-WGS in seventeen members of this pedigree, including three individuals with a confirmed diagnosis of RP. Sequencing data were processed using Illumina's DRAGEN pipeline and filtered using Illumina's genotype quality score metric (GQX). The resulting variants were analyzed using Expert Variant Interpreter (eVai) from enGenome as a prioritization tool. A nonsense known mutation (c.1625C > G; p.Ser542*) in exon 4 of the RP1 gene emerged as the most likely causal variant. We identified two homozygous carriers of this variant among the three sequenced RP cases and three heterozygous individuals with sufficient coverage of the RP1 locus. Our data show the utility of combining pedigree information with XLC-WGS as a cost-effective approach to identify disease-causing variants.

Concurrence of Rheumatoid Arthritis and Ankylosing Spondylitis: Analysis of Seven Cases and Literature Review.

Introduction: The association of rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in a single patient is a rarely described phenomenon. AS and RA are conditions that can have a high impact on the morbidity and mortality of patients. Methods: We described the clinical, epidemiological, analytical, and radiological characteristics of 81 patients with concomitant diagnosis of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Of these patients, seven were diagnosed at our hospital. A literature review was carried out using Medline, Embase, Scopus, and virtual hospital libraries, including the period from January 1950 to April 2020. Results: Regarding the results, 71% of the patients were men, with a mean age of 53 years (±14.83). RA was the first disease diagnosed in 52% of the cases. Approximately 53% of the patients had rheumatoid nodules, and 83% reported inflammatory lumbar pain during their evaluation. Erosions were observed on radiographs of the hands and/or feet in 85% of the cases, and almost all the patients (80/81) had sacroiliitis on imaging studies. Approximately 92% of the cases were rheumatoid factor (RF) positive and 90% HLA B-27 positive. Conclusions: The coexistence of RA and AS is highly uncommon. With the data obtained in this review, it seems that there exist erosive radiological patterns, positivity for RF, involvement of the axial skeleton, and rheumatoid nodules at a higher frequency than those patients with a single diagnosis of the two entities. More data are needed to corroborate this association.