ABSTRACT
A large proportion of patients with idiopathic spermatogenic failure (SPGF; oligozoospermia or nonobstructive azoospermia [NOA]) do not receive a diagnosis despite an extensive diagnostic workup. Recent evidence has shown that the etiology remains undefined in up to 75% of these patients. A number of genes involved in germ-cell proliferation, spermatocyte meiotic divisions, and spermatid development have been called into play in the pathogenesis of idiopathic oligozoospermia or NOA. However, this evidence mainly comes from case reports. Therefore, this study was undertaken to identify the molecular causes of SPGF. To accomplish this, 15 genes (USP9Y, NR5A1, KLHL10, ZMYND15, PLK4, TEX15, TEX11, MEIOB, SOHLH1, HSF2, SYCP3, TAF4B, NANOS1, SYCE1, and RHOXF2) involved in idiopathic SPGF were simultaneously analyzed in a cohort of 25 patients with idiopathic oligozoospermia or NOA, accurately selected after a thorough diagnostic workup. After next-generation sequencing (NGS) analysis, we identified the presence of rare variants in the NR5A1 and TEX11 genes with a pathogenic role in 3/25 (12.0%) patients. Seventeen other different variants were identified, and among them, 13 have never been reported before. Eleven out of 17 variants were likely pathogenic and deserve functional or segregation studies. The genes most frequently mutated were MEIOB, followed by USP9Y, KLHL10, NR5A1, and SOHLH1. No alterations were found in the SYCP3, TAF4B, NANOS1, SYCE1, or RHOXF2 genes. In conclusion, NGS technology, by screening a specific custom-made panel of genes, could help increase the diagnostic rate in patients with idiopathic oligozoospermia or NOA.
ABSTRACT
The sacroiliac joints connect the base of the sacrum to the ilium. When inflamed, they are suspected to cause low back pain. Inflammation of the sacroiliac joints is called sacroiliitis. The severity of the pain varies and depends on the degree of inflammation. Sacroiliitis is a hallmark of seronegative spondyloarthropathies. The presence or absence of chronic sacroiliitis is an important clue in the diagnosis of low back pain. This article aims to provide a concise overview of the anatomy, physiology, and molecular biology of sacroiliitis to aid clinicians in the assessment and management of sacroiliitis. For this narrative review, we evaluated articles in English published before August 2019 in PubMed. Then, we selected articles related to the painful manifestations of the sacroiliac joint. From the retrieved articles, we found that chronic sacroiliitis may be caused by various forms of spondyloarthritis, such as ankylosing spondyloarthritis. Sacroiliitis can also be associated with inflammatory bowel disease, Crohn’s disease, gout, tuberculosis, brucellosis, and osteoarthritis, indicating common underlying etiological factors. The pathophysiology of sacroiliitis is complex and may involve internal, environmental, immunological, and genetic factors. Finally, genetic factors may also play a central role in progression of the disease. Knowing the genetic pre-disposition for sacroiliitis can be useful for diagnosis and for formulating treatment regimens, and may lead to a substantial reduction in disease severity and duration and to improved patient performance.