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Some subtypes of hereditary spastic paraplegia (HSP), especially with autosomal recessive inheritance (AR-HSP), have been reported rarely. In this study, we report the clinical features and molecular results of three unrelated Iranian patients with rare subtypes of HSP, including SPG76, SPG56, and SPG69; thereafter, we compare them to other reported cases. Three patients who were clinically diagnosed with HSP and born to consanguineous parents underwent molecular assessment by whole-exome sequencing (WES), followed by Sanger sequencing and co-segregation analysis. Two patients carried biallelic pathogenic variants in CAPN1, or CYP2U1, resulting in SPG76, and SPG56, respectively. Additionally, another patient presented with a variant of uncertain significance (VUS) in the gene associated with SPG69, known as RAB3GAP2. Variants of CAPN1 and RAB3GAP2 are novel while the CYP2U1 variant has been previously reported. The patient with the RAB3GAP2 variant is the second reported SPG69 case. Our findings emphasize that the rare forms of AR-HSP may be more prevalent in communities with a high rate of consanguineous marriages, and WES can be a highly effective tool for identifying pathogenic variants in these communities. Also, the CYP2U1 variant seems to be a founder mutation because it was previously reported in 8 patients of three families from the Middle East. These results expand the variant spectrum of the CAPN1 and RAB3GAP2 genes. Also, given the association of variants in CAPN1 and RAB3GAP2 with a diverse array of phenotypes, we propose the use of the terms "CAPN1-related disorders" and "RAB3GAP2-related disorders" as alternatives to HSP76 and HSP69, respectively. [ABSTRACT FROM AUTHOR]

Background: We conducted this study to determine the safety and evidence of effectiveness of SeptimebTM among patients with COVID-19. Methods: An uncontrolled phase II clinical trial with SeptimebTM was implemented in Imam Khomeini Hospital as a before-and-after trial during May to October 2020. Considering the inclusion and exclusion criteria, 33 patients with COVID-19 were treated using SeptimebTM. The patients received the anti-inflammatory drug 150 mg /10 ml /IV infusion SeptimebTM on the first day and then 300 mg /20 ml / IV infusion from the second day onwards for at least 2 days and up to 13 days based on the improvement of clinical symptoms and laboratory findings in addition to treatment which were selected according to the national protocol. The patients were then evaluated for the treatment efficacy and side effects. Adherence to treatment, clinical observations, and side effects were recorded before and after the treatment. Results: The herbal drug SeptimebTM was injected in phase two of an uncontrolled clinical trial on 33 patients with COVID-19 in Imam Khomeini Hospital in Tehran as a before-and-after trial. The number of new cases admitted to the Intensive Care Unit (ICU) and the new need to Non-Invasive Ventilation (NIV) ecreased compared to before the treatment. Also, blood oxygen saturation and platelet count increased. Conversely, CRP, ESR, and ferritin levels decreased (p<0.05). Besides, SeptimebTM did not show any serious side effects except recurrent thrombophlebitis during the treatment. Conclusion: We found some evidence regarding the efficacy of this drug and its low amount of short term side effects. The investigators recommend conducting the third phase of the clinical trial. [ABSTRACT FROM AUTHOR]

Background: The study of Y-chromosomal variations provides valuable insights into male susceptibility in certain diseases like cardiovascular disease (CVD). In this study, we analyzed paternal lineage in different Iranian ethnic groups, not only to identify developing medical etiology, but also to pave the way for gender-specific targeted strategies and personalized medicine in medical genetic research studies. Methods: The diversity of eleven Iranian ethnic groups was studied using 27 Y-chromosomal short tandem repeat (Y-STR) haplotypes from Y-filer® Plus kit. Analysis of molecular variance (AMOVA) based on pair-wise RST along with multidimensional scaling (MDS) calculation and Network phylogenic analysis was employed to quantify the differences between 503 unrelated individuals from each ethnicity. Results: Results from AMOVA calculation confirmed that Gilaks and Azeris showed the largest genetic distance (RST = 0.35434); however, Sistanis and Lurs had the smallest considerable genetic distance (RST = 0.00483) compared to other ethnicities. Although Azeris had a considerable distance from other ethnicities, they were still close to Turkmens. MDS analysis of ethnic groups gave the indication of lack of similarity between different ethnicities. Besides, network phylogenic analysis demonstrated insignificant clustering between samples. Conclusion: The AMOVA analysis results explain that the close distance of Azeris and Turkmens may be the effect of maledominant expansions across Central Asia that contributed to historical and demographics of populations in the region. Insignificant differences in network analysis could be the consequence of high mutation events that happened in the Y-STR regions over the years. Considering the ethnic group affiliations in medical research, our results provided an understanding and characterization of Iranian male population for future medical and population genetics studies. [ABSTRACT FROM AUTHOR]

Some subtypes of hereditary spastic paraplegia (HSP), especially with autosomal recessive inheritance (AR-HSP), have been reported rarely. In this study, we report the clinical features and molecular results of three unrelated Iranian patients with rare subtypes of HSP, including SPG76, SPG56, and SPG69; thereafter, we compare them to other reported cases. Three patients who were clinically diagnosed with HSP and born to consanguineous parents underwent molecular assessment by whole-exome sequencing (WES), followed by Sanger sequencing and co-segregation analysis. Two patients carried biallelic pathogenic variants in CAPN1, or CYP2U1, resulting in SPG76, and SPG56, respectively. Additionally, another patient presented with a variant of uncertain significance (VUS) in the gene associated with SPG69, known as RAB3GAP2. Variants of CAPN1 and RAB3GAP2 are novel while the CYP2U1 variant has been previously reported. The patient with the RAB3GAP2 variant is the second reported SPG69 case. Our findings emphasize that the rare forms of AR-HSP may be more prevalent in communities with a high rate of consanguineous marriages, and WES can be a highly effective tool for identifying pathogenic variants in these communities. Also, the CYP2U1 variant seems to be a founder mutation because it was previously reported in 8 patients of three families from the Middle East. These results expand the variant spectrum of the CAPN1 and RAB3GAP2 genes. Also, given the association of variants in CAPN1 and RAB3GAP2 with a diverse array of phenotypes, we propose the use of the terms "CAPN1-related disorders" and "RAB3GAP2-related disorders" as alternatives to HSP76 and HSP69, respectively., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: This research was conducted in accordance with the principles outlined in the Declaration of Helsinki and received approval from the ethics board of the University of Social Welfare and Rehabilitation Sciences (IR.USWR.REC.1400.053) in Iran. Consent to participate: Informed consent was obtained from the patients or their guardians to participate in the project. Consent to publication: The authors affirm that patients or their guardians provided signed informed consent to publish the data of the project., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)