Fahimeh Piryaei

Biallelic variants in the KARS1 gene, encoding lysyl-tRNA synthetase, are responsible for autosomal recessive disorders such as infantile-onset progressive leukoencephalopathy with or without deafness (LEPID; OMIM #619147) and nonsyndromic hearing loss (DFNB89). Common features of LEPID include sensorineural hearing loss, developmental delay, and leukoencephalopathy, but dysmorphic facial features and cardiac anomalies are not commonly reported. This study presents the first documented LEPID case in Iran, expanding the phenotypic and genetic spectrum of KARS1-related disorders. Whole exome sequencing (WES) was performed on a two-year-old Iranian boy from non-consanguineous parents, without a positive history of any neurologic conditions. Identified variants were validated by Sanger sequencing, with familial segregation analysis. Moreover, a literature review of 41 KARS1-related cases was conducted to compare clinical and genetic findings. WES identified two compound heterozygous KARS1 variants (NM_005548.3): c.959G > A (p.Arg320His) and c.2T > C (p.Met1Thr), previously reported and novel, respectively, both of which were classified as likely pathogenic according to the American College of Medical Genetics and Genomics criteria. The patient exhibited typical LEPID features (sensorineural hearing loss, developmental delay, seizures, leukoencephalopathy) alongside unprecedented dysmorphic facial features (e.g., synophrys, pointed triangular chin) and cardiac anomalies (pulmonary stenosis, atrial septal defect). Literature review confirmed these dysmorphic features as novel, absent in prior cases, with cardiac involvement in a limited number of patients. This study highlights a novel KARS1 variant and an expanded phenotypic spectrum of LEPID, emphasizing the role of WES in diagnosing rare disorders even in non-consanguineous marriages. These findings advocate for broader phenotypic recognition and functional studies to elucidate KARS1’s role in neurodevelopmental, craniofacial, and cardiac abnormalities.

Mahmutoglu AM, et al. World J Mens Health. 2025 Apr;43:e22. https://doi.org/10.5534/wjmh.250006

Rapid growth of the aquaculture industry is hampered by infectious diseases in marine invertebrates, causing economic losses. Marine invertebrate cell cultures offer tools to evaluate biological properties and cellular responses in different conditions. Long-term culture aims to isolate tissue-specific cells and identify bioactive compounds from stem cells. Echinometra mathaei, known as Persian Gulf sea urchin, has lots of benefits in various fields including aquaculture, embryology, and evolutionary biology. However, its cell culture faces challenges due to poorly characterized microenvironmental and specific cultivation requirements. This study aims to establish and optimize a long-term cell culture for coelomocyte derived from E. mathaei, focusing on the characterization of microenvironment conditions to overcome the limitations of current marine invertebrate cell culture. After the collection of E. mathaei from Lark Island, Persian Gulf, Iran, and their acclimatization in artificial seawater, coelomocytes were isolated from different sources including the coelomic fluid, the coelomic epithelium, and the axial organ. Various cell dissociation methods, culture media, growth supplements, culture dishes, and physical conditions were tested to determine optimal conditions for coelomocyte in vitro culture. Moreover, coelomocytes were differentiated to pigment-producing cells, and naphthoquinone pigments were extracted and identified using spectrophotometry. Light microscopy identified several coelomocyte types, including petaloid, filopodial, vibratile cells, and spherulocytes. The HCCM medium supplemented with coelomic fluid proved most effective for cell growth and viability. Moreover, coelomic fluid is the best culture media for differentiation of coelomocyte into the cell producing naphthoquinone pigments. These findings contribute to developing in vitro cell culture methods for sea urchin, providing a foundation for further research on sea urchin immunology, cell biology, and cellular responses to pathogens and other biological stress.

Background: DYT‐PRKRA is a rare, autosomal recessive movement disorder caused by mutations in the PRKRA gene. While PRKRA mutations are recognized in DYT‐PRKRA, a significant number of identified variants are still classified as “variant of uncertain significance” (VUS). Objective: In this study we identified a causative variant previously reported as a VUS. Methods: A 4.5‐year‐old female born to consanguineous, healthy parents presented with progressive neurodevelopmental regression, similar to two affected relatives. Whole‐exome sequencing was performed, and segregation analysis was conducted across two generations. Results: A homozygous PRKRA c.74A>G (p.Lys25Arg) variant co‐segregated with the DYT‐PRKRA phenotype. Unaffected family members were identified as heterozygous carriers. Conclusions: This is the first report of DYT‐PRKRA in the Iranian population. Strong evidence from familial segregation and in silico analyses support the reclassification of this variant to likely pathogenic. This reclassification has significant implications for the diagnosis and genetic counseling of families affected by DYT‐PRKRA. © 2025 International Parkinson and Movement Disorder Society.

Background Nanovesicles derived from botanical sources have garnered significant attention in the medicine and pharmacology due to their straightforward and efficient scaling methods for isolation. Allium cepa (A. cepa), or common red onion, has a long history in traditional medicine, primarily for its anti-inflammatory and antioxidant effects. Despite the growing interest, the biological activity of red onion-derived exosome-like nanovesicles (RDNVs) remains inadequately explored. In this context we tried to prepare nanovesicles from red onion juice and their therapeutic potential in a full-thickness skin wound animal model. Methods and results Following isolation and characterization of RDNVs, their anti-oxidant capacity was assessed via 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide dismutase (SOD) activity assays. A single, full-thickness, circular wound was created on the backs of C57BL/6 mice. Thirty mice were randomly administrated with PBS (control), red onion ethanolic extract, and RDNV. Wound healing parameters such as re-epithelialization, antioxidant status, and inflammation were evaluated at Days 4 and 7 post-wounding. The cup-shaped RDNVs isolated from A. cepa showed significant antioxidant activity and effectively polarized M1 phenotype to M2 phenotype macrophages compared to control group. Furthermore, the pro-inflammatory genes expression was significantly reduced in both RDNV and onion extract-treated groups (p-value < 0.01). Histological analysis revealed improved granulation tissue formation and re-epithelialization, and significant reduction in inflammatory cells in RDNV-treated wounds. Conclusions The findings of this study support the idea that RDNVs shed new light on skin wound management through antioxidant and anti-inflammatory activity and accelerating wound healing.

Background and Objective: Small non-coding RNAs (sncRNAs) have been studied in the male reproductive system. One of the most important small RNAs (sRNAs) investigated in spermatogenesis is piRNA. This study performed a comprehensive analysis and comparison of the expression profiles of novel sRNA sequences, which are predicted to be piRNAs, in male testicular tissue. Materials and Methods: The GSE248576 dataset in NCBI-GEO was used to discover novel sequences. Subsequently, potential target genes of the discovered sequences were predicted using the Miranda tool. Finally, regulatory pathways related to spermatogenesis were obtained using bioinformatics tools. Results: In this study, 208 novel sRNA sequences were identified as piRNAs in male testicular tissue that have not been reported in small sequence databases so far. KEGG and Reactome pathways, protein-protein interaction analysis, significant terms related to the regulatory processes of mitosis and meiosis, and cell growth in gametogenesis were identified in the gene ontology analysis. Conclusion: The newly found sRNA sequences and their predicted target genes in this study could be promising candidates for investigating their role in impaired spermatogenesis as an infertility phenotype in men.

Male infertility has remained idiopathic in a remarkable proportion of all cases. Gonadal expression of PIWI-interacting RNAs (piRNAs) has been shown to be vital to normal spermatogenesis, as they are expressed in almost all types of testicular germ cells. These molecules and their related Piwi proteins strictly regulate transposable elements’ activity and gene expression. We aimed to identify dysregulated piRNAs in idiopathic non-obstructive azoospermic (NOA) testis by global expression analysis. Testis tissue samples from 18 azoospermic patients (ten NOA and eight OA) were studied by small RNA sequencing. To validate high-throughput sequencing data, quantitative real-time polymerase chain reactions for two differentially altered piRNAs were performed. Bioinformatics analyses were undertaken to identify pathways affected by piRNA dysregulation. In the NOA group, 1328 piRNAs were identified to be differentially expressed, of which 1322 were downregulated and 6 were upregulated. Bioinformatics analysis corroborated the involvement of dysregulated piRNA in spermatogenesis. We also identified 64 clusters of differentially expressed piRNAs, of which 42 clusters had a minimum of ten absolute piRNA hits. Our study suggests that piRNAs show significant dysregulation in infertility. Their target genes play a role in their self-biogenesis, probably by regulating their own production through a feedback mechanism. The downregulated piRNAs may find value as biomarkers for the presence of spermatozoa in the testis of azoospermic individuals, while the upregulated piRNAs are great candidates for further investigation of their precise functions in spermatogenesis.

Background: Robertsonian translocations (RobTs) are one of the major chromosomal abnormalities which lead to spontaneous abortion. They occur in the human population at the rate of 1 in 1000 live infants. In this paper, a family carrying one of the rare RobTs was presented and some features of all kinds of RobTs were reviewed. Case Presentation: A couple with a history of three miscarriages was referred to Omid Health Clinic of Hamadan, Iran. The karyotype of the woman was 45,XX, rob(14;15)(q10;q10) and she exhibited phenotypically good health. Karyotype analysis of proband’s uncle and his wife with a consanguineous marriage revealed that they were both carriers of rob(14;15). This couple had six offspring, three of which were dead, and the other three were alive with a normal phenotype. Besides, this couple had an unborn child, with a karyotype of 44,XX,rob(14;15)(q10;q10). Conclusion: These observations showed that genetic counseling, pedigree, and chromosomal analysis are needed to discover the cause of spontaneous abortion, stillbirth, congenital anomalies, sudden infant death syndrome (SIDS), etc. Moreover, families carrying RobTs would be offered prenatal diagnosis screening tests and, if necessary, assisted reproductive technology methods to assist with preimplantation genetic test for structural rearrangement (PGT-SR) reproduction.

Introduction. The etiology of male infertility characterized by non‐obstructive azoospermia is largely unknown, especially at the molecular level. Identifying dysregulated microRNAs (miRNAs) in male infertility would be useful to achieve a more profound understanding of its pathogenesis. Methods. Small RNA sequencing was performed on the testicular tissues of 10 nonobstructive azoospermic patients with the Sertoli cell only syndrome (SCOS) and 8 obstructive azoospermic individuals with normal spermatogenesis. The expressions of two dysregulated miRNAs were validated by quantitative real‐time polymerase chain reaction, confirming the results obtained by sequencing analysis. Bioinformatic analysis was undertaken to identify the main pathways impaired in complete spermatogenic failure. Results. A total of 136 miRNAs were detected to be differentially expressed in the Sertoli cell only syndrome group in comparison with the obstructive azoospermia group. Bioinformatic analysis suggested that the altered miRNAs were substantially involved in pathways related to spermatogenesis. Conclusions. Our study investigates the entire profile of miRNAs with emphasis on the crucial role of miRNAs in idiopathic Sertoli cell only syndrome, suggesting potential targets for employing molecular therapeutic strategies in the treatment of spermatogenic failure.