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Genetic work-up for the rare new mutations causing musculoskeletal and spine pain

1.1. Background: Spine pain is widespread due to degenerative disc disease and facet arthropathy. Most patients improve with supportive conservative care measures, including non-steroidal anti-inflammatories, physical therapy, short episodes of rest, and activity modification. Medical and interventional pain manage ment is reserved for those patients who do not improve within 4 to 6 weeks of standard spine care managed within the primary care setting, after which patients are typically referred to a specialist. Genetic conditions are rarely considered early in the differential diagnosis and may be easily missed in non-responsive patients. 1.2. Methods: We briefly de-scribe two illustrative cases of pa tients with a history of chronic musculoskeletal and spinal pain, whose delayed diagnosis led to improper utilization of medical resources until they were diagnosed correctly and targeted person alized care for their painful syndromes could be instituted. 1.3. Results: After a long history of physiotherapy for sever al years to alleviate muscular and spine pain, a patient with lack of proper control of the trunk and leg muscles causing difficul ties with getting up from a sitting position, walking, and climbing stairs was diagnosed with a new mutation in the KLHL40 gene associated with the pain syndrome of Nemaline Myopathy. A sec ond case a severe scoliosis with short femur leading to dwarfism through sonography investigations was diagnosed via mutation in exon 5 of the FGFR3 gene by WES and Sanger sequencing tests. An aborted fetus whose parents did not carry the mutant allele as sociated with Autosomal dominant thanatophoric dysplasia type I due to a de novo mutation of the FGFR3 gene associated with increased sensitivity of nociceptors such as TNF-α. 1.4. Conclusions: Genetic factors may play a more significant role in unrelenting musculoskeletal and spinal pain syndromes in indi viduals unresponsive to standard conservative care measures than previously thought. Genetic screening, counseling, and a combi nation of targeted interventions aimed at alleviating the harmful effect of the underlying gene defect and the disability associated with painful conditions of the musculoskeletal system affecting lo- 2 Volume 10 Issue 19 -2023 Case Report comotion and spinal deformity and balance should be considered early on mainly if the index of suspicion for an underlying genetic condition is high.

Investigation of Methylation Levels in COMT Gene Promoter among Smokers and Opium Addicted Individuals Undergoing Methadone Treatment

1.1. Background: Previous studies have demonstrated that the COMT gene is associated with alcohol, nicotine, and illicit sub stances. The aim of the present study was to examine the methyla tion status of a remarkable region in the COMT gene promoter in methadone-treated smokers and addicts. Methods: All male sam ples, including 30 smokers, 30 opium addicts receiving methadone treatment, and 30 healthy individuals, had their DNAs extracted from their whole blood and processed with a sodium bisulfite kit. 61 CpG dinucleotides were included in the study region and were sequenced. 1.2. Results: Results represented that within these CpG sites, only 25 CpG sites in the addicted group and 22 in the smoker group compared to the healthy controls indicated different methylation levels; however, none of these CpG sites had a statistically signif icant difference (P=0.281 and P= 0.329, respectively). The mean age of opium-addicted individuals and healthy controls had signif icant differences between the two groups (P=0.017). Demograph ical results revealed that methadone dosage correlated with the resident situation and libido dysfunction (P=0.032 and P=0.003, respectively). 1.3. Conclusion: In conclusion, the investigation of methylation levels at COMT gene promoter had no noticeable significance among smokers and methadone maintenance treatment (MMT) patients compared to the healthy controls; moreover, methadone dosage had significant correlations with demographical statuses in the MMT group.

A new de novo mutation in HTRA1 gene associated with painful Ataxia, developmental delay, and autistic behaviors symptoms in an Iranian boy through Whole Exome Sequencing followed by homology modeling

1.1. Introduction: Due to the insufficiency of understanding about Dominant Arteriopathy with Subcortical Infarcts and Leukoen cephalopathy (CADASIL) in general clinical studies, the process of diagnosis for most CADASIL patients is complex and often prolonged. The disease’s symptomatic heterogeneity, which hap pens frequently even among family members, increases the com plexity of diagnosis. 1.2. Methods: In vitro analysis was carried out by Whole Exome Sequencing (WES) for a 2-year-old boy. He had ataxia, develop mental delay, delayed speech and language development, and au tistic behaviors. Mutational confirmations were also done on both of his parents to find the genotypes. Also, bioinformatics predic tions were performed by SWISS-MODEL, ProSA, Molprobity, and superimposition through MatchMaker in Chimera ver. 1.16. 1.3. Results: WES analysis uncovered a novel de novo missense mutation in the HTRA1 gene (exon1:c.320C>T:p.A107V) in the case. Mutation conformations documented the homozygosity of the normal allele in both of the case’s parents. Superimposition predictions suggested two beta-sheet unfolded in the mutant model (T allele or Val107). 1.4. Conclusion: Consequently, in an autosomal dominant pattern of genetic inheritance, the current study described a novel de novo mutation in the HTRA1 gene (A107V) associated with neurologi cal features such as painful ataxia, and developmental and speech delays. Pain management is necessary in this case and future cases with the same symptoms.

New frameshift in PAX6 and missense mutation in EYA1 gene found by Whole Exome Sequencing associated with severe eye impairments in an Iranian Family

1.1. Introduction: Previous studies have examined the impacts of PAX6 mutations on a wide range of eye impairments. Because of the PAX6 protein’s binding functions, alterations in its structure may prevent it from correctly connecting with the DNA molecule. 1.2. Materials and Methods: Whole Exome Sequencing [WES] was used to perform in vitro analysis on a 30-year-old woman who sent to a genetic laboratory for PND. Her spouse had clear seri ous vision problems. To determine the genotypes, both her spouse and her husband’s sister underwent mutation confirmation tests. In silico predictions were also conducted using SWISS-MODEL, ProSA, Molprobity, and SuperPose. 1.3. Results: WES analysis revealed a new frameshift of the PAX6 gene [exon5:c.11delG:p.S4fs] and a missense mutation in the EYA1 gene [exon14:c.C1309T:p.R437C] in a 30-year-old wom an. Mutation conformations represented the heterozygosity for the PAX6 mutation in both the husband and his sister. Further in silico predictions showed a distinct deleted part of PAX6 resulted from the frameshift mutation compared with the normal allele. 1.4. Conclusion: Altogether, for the first time, our report intro duced two new mutations in the PAX6 and EYA1 genes associated with severe signs of anterior segmental dysgenesis with cataract and corneal dystrophy in an Iranian family based on an autosomal dominant pattern of genetic inheritance.

Bacteremia due to Serratia Rubidaea in ICU: Case series

Bacteremia due to S.Rubidaea is rarely described comparing with other species of Enterobacteriacae. It interests immunocompro mised patients undergoing invasive procedures. Herein, we report four cases of bacteraemia due to this pathogen in patients admitted in ICU for ketoacidosis with history of diabetes mellitus.Common ly, a catheter-related infection complicated with deep vein throm bosis was present. Catheter site was femoral in all four cases. All patients were female. Commonly, a poorly-tolerated fever was the main clinical manifestation. The pathogen was isolated in several peripheral blood cultures (>4) for the same patient with the same profile in all four cases.

Frequency of pin tract infection among patients with tibia fracture treated with AO external fixator

1.1. Introduction: The management of open tibial fractures re mains a challenge for the orthopedic surgeons as various post-op erative complications are associated with external fixation of tibia fracture. 1.2. Objectives: To determine frequency of pin track infection among patients with tibia fracture treated with AO external fixator. 1.3. Material and Methods: This Descriptive case series study was carried out Department of Orthopedics, Medical Teaching In stitute Lady Reading Hospital from February , 2022 till December, 2022 on 110 Patients, aged 20 to 60 years of either gender with open fracture tibia Gustillo-Anderson type II or type IIIA were enrolled using non-probability consecutive sampling technique. All patients with tibia fracture underwent AO external fixation and reduction. Frequency of pin tract infection was noted. Data was entered and analyzed using SPSS 22. 1.4. Results: In our study 110 patients were enrolled with mean age of 36.7±11.5 years. There were 56.4% males and 43.6% fe male patients. Mean duration of injury was 14.6±7.6 hours. Hy pertension was present in 30.9% patients. Diabetes was present in 16.4% patients. Smoking was present in 36.4% patients. Obesity was present in 41.6% patients. Pin tract infection was present in 16.4% patients. 1.5. Conclusion: Our study concludes that the incidence of pin tract infection is high.

Investigation of Methylation Levels in OPRK1 Gene Promoter among Smokers and Opium-Addicts underwent Methadone Maintenance Treatment

1.1. Background: Previous studies reported the association of the OPRK1 gene with illicit substances, nicotine, and alcohol. The present study aimed to look at the methylation levels of OPRK1 gene promoter among smokers and addicts who underwent metha done maintenance treatment (MMT). 1.2. Methods: DNAs were extracted from the whole blood of all male samples including 30 smokers, 30 opium-addicted individu als undergoing methadone treatment, and 30 healthy people, and they were treated with a sodium bisulfite kit. The studied region included 53 CpG dinucleotides investigated by sequencing tech nique. 1.3. Results: Results of methylation levels in addicted individuals who underwent MMT compared with healthy people showed no difference. Also, there was no change in any CpG sites of OPRK1 gene promoter in both smokers and compared healthy controls. There was a significant difference in the mean age between opi um-dependent people and healthy controls (P=0.017). According to the findings of the statistical analysis, resident situation and li bido dysfunction were associated with methadone dose (P=0.032 and P=0.003, respectively). 1.4. Conclusion: Altogether, the study of methylation levels at OPRK1 gene promoter was not significant among smokers and in dividuals who underwent MMT compared to the healthy controls; additionally, methadone dosage had significant associations with demographical statuses in the MMT group.

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