Iranian Family Research Articles

Genetic change investigation in DOCK1 gene in an Iranian family with sign and symptoms of temporomandibular joint disorder (TMD).

Temporomandibular joint disorder (TMD) is a complex condition with pain and dysfunction in the temporomandibular joint and related muscles. Scientific evidence indicates both genetic and environmental factors play a crucial role in TMD. In this study, we aimed to discover the genetic changes in individuals from 4 generations of an Iranian family with signs and symptoms of TMD and malocclusion Class III. Whole Exome Sequencing (WES) was performed in 4 patients (IV-8, IV-9, V-4, and V-6) with TMD according to (DC/TMD), along with skeletal Class III malocclusion. Then, PCR sequencing was performed on 23 family members to confirm the WES. In the present study, WES results analysis detected 6 heterozygous non-synonymous Single Nucleotide Variants (SNVs) in 5 genes, including CRLF3, DNAH17, DOCK1, SEPT9, and VWDE. A heterozygous variant, c.2012T > A (p.F671Y), in Exon 20 of the DOCK1 (NM_001290223.2) gene was identified. Then, this variant was investigated in 19 other members of the same family. PCR-Sequencing results showed that 7/19 had heterozygous TA genotype, all of whom were accompanied by malocclusion and TMD symptoms and 12/19 individuals had homozygous TT genotype, 9 of whom had no temporomandibular joint problems or malocclusion. The remaining 3 showed mild TMD clinical symptoms. The 5 other non-synonymous SNVs of CRLF3, DNAH17, SEPT9, and VWDE were not considered plausible candidates for TMD. The present study identified a heterozygous nonsynonymous c.2012T > A (p.F671Y) variant of the DOCK1 gene is significantly associated with skeletal class III malocclusion, TMD, and its severity in affected individuals in the Iranian pedigree. The role of genetic factors in the development of TMD has been described. The present study identified a nonsynonymous variant of the DOCK1 gene as a candidate for TMD and skeletal class III malocclusion in affected individuals in the Iranian pedigree.

Exploring maternal perceptions of critical digital engagement practices in Iranian children

ABSTRACT Limited studies exist that demonstrate the way that children show critical digital literacies such as expressing their voices through digital technologies at home. To explore this further, the present study draws on Mirra et al.’s framework (2018) to analyze the types of critical digital engagement with digital technologies. Critical digital engagement refers to different critical digital literacy practices used to achieve a particular goal such as critically evaluating, creating, sharing, and designing digital resources. In this study, we recruited five Iranian families involving five mothers and six children aged six to seven. The data collection process involved semi-structured interviews with the children and mothers, demographic profiles, and collecting photos of the children’s home digital literacy practices. Having used deductive coding, we report on several differences and similarities between children’s digital literacy practices and their types of critical engagement such as critical digital consumption, production, distribution, and invention. These similarities and differences may stem from political, historical, social, cultural, and economic influences in the Iranian context. Understanding the way that children express their voices through digital technologies can give invaluable insights for policymakers, teachers, and parents to better support children in becoming engaged digital citizens.

A novel start-loss mutation of the SLC29A3 gene in a consanguineous family with H syndrome: clinical characteristics, in silico analysis and literature review

BackgroundThe SLC29A3 gene, which encodes a nucleoside transporter protein, is primarily located in intracellular membranes. The mutations in this gene can give rise to various clinical manifestations, including H syndrome, dysosteosclerosis, Faisalabad histiocytosis, and pigmented hypertrichosis with insulin-dependent diabetes. The aim of this study is to present two Iranian patients with H syndrome and to describe a novel start-loss mutation in SLC29A3 gene.MethodsIn this study, we employed whole-exome sequencing (WES) as a method to identify genetic variations that contribute to the development of H syndrome in a 16-year-old girl and her 8-year-old brother. These siblings were part of an Iranian family with consanguineous parents. To confirmed the pathogenicity of the identified variant, we utilized in-silico tools and cross-referenced various databases to confirm its novelty. Additionally, we conducted a co-segregation study and verified the presence of the variant in the parents of the affected patients through Sanger sequencing.ResultsIn our study, we identified a novel start-loss mutation (c.2T > A, p.Met1Lys) in the SLC29A3 gene, which was found in both of two patients. Co-segregation analysis using Sanger sequencing confirmed that this variant was inherited from the parents. To evaluate the potential pathogenicity and novelty of this mutation, we consulted various databases. Additionally, we employed bioinformatics tools to predict the three-dimensional structure of the mutant SLC29A3 protein. These analyses were conducted with the aim of providing valuable insights into the functional implications of the identified mutation on the structure and function of the SLC29A3 protein.ConclusionOur study contributes to the expanding body of evidence supporting the association between mutations in the SLC29A3 gene and H syndrome. The molecular analysis of diseases related to SLC29A3 is crucial in understanding the range of variability and raising awareness of H syndrome, with the ultimate goal of facilitating early diagnosis and appropriate treatment. The discovery of this novel biallelic variant in the probands further underscores the significance of utilizing genetic testing approaches, such as WES, as dependable diagnostic tools for individuals with this particular condition.

Whole genome sequencing identifies a homozygous splicing variant in TDRKH segregating with non-obstructive azoospermia in an Iranian family.

Non-obstructive azoospermia (NOA) resulting from primary spermatogenic failure represents one of the most severe forms of male infertility, largely because therapeutic options are very limited. Beyond their diagnostic value, genetic tests for NOA also hold prognostic potential. Specifically, genetic diagnosis enables the establishment of genotype-testicular phenotype correlations, which, in some cases, provide a negative predictive value for testicular sperm extraction (TESE), thereby preventing unnecessary surgical procedures. In this study, we employed whole-genome sequencing (WGS) to investigate two generations of an Iranian family with NOA and identified a homozygous splicing variant in TDRKH (NM_001083965.2: c.562-2A>T). TDRKH encodes a conserved mitochondrial membrane-anchored factor essential for piRNA biogenesis in germ cells. In Tdrkh knockout mice, de-repression of retrotransposons in germ cells leads to spermatogenic arrest and male infertility. Previously, our team reported TDRKH involvement in human NOA cases through the investigation of a North African cohort. This current study marks the second report of TDRKH's role in NOA and human male infertility, underscoring the significance of the piRNA pathway in spermatogenesis. Furthermore, across both studies, we demonstrated that men carrying TDRKH variants, similar to knockout mice, exhibit complete spermatogenic arrest, correlating with failed testicular sperm retrieval.

A Comprehensive Overview of NF1 Mutations in Iranian Patients.

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations in the NF1 gene. This disorder shows nearly complete penetrance and high phenotypic variability. We used the whole-exome sequencing technique to identify mutations in 32 NF1 cases from 22 Iranian families. A total of 31 variants, including 30 point mutations and one large deletion, were detected. In eight cases, variants were inherited, while they were sporadic in the remaining. Seven novel variants, including c.5576T > G, c.6658_6659insC, c.2322dupT, c.92_93insAA, c.4360C > T, c.3814C > T, and c.4565_4566delinsC, were identified. The current study is the largest in terms of the sample size of Iranian NF1 cases with identified mutations. The results can broaden the spectrum of NF1 mutations and facilitate the process of genetic counseling in the affected families.

Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsia

BackgroundAutosomal recessive non-syndromic hearing loss (NSHL) and cone dystrophies (CODs) are highly genetically and phenotypically heterogeneous disorders. In this study, we applied the whole exome sequencing (WES) to find the cause of HL and COD in an Iranian consanguineous family with three affected individuals.MethodsThree members from an Iranian consanguineous family who were suffering from NSHL and visual impairment were ascertained in this study. Comprehensive clinical evaluations and genetic analysis followed by bioinformatic and co-segregation studies were performed to diagnose the cause of these phenotypes. Data were collected from 2020 to 2022.ResultsAll cases showed congenital bilateral NSHL, decreased visual acuity, poor color discrimination, photophobia and macular atrophy. Moreover, cornea, iris and anterior vitreous were within normal limit in both eyes, decreased foveal sensitivity, central scotoma and generalized depression of visual field were seen in three cases. WES results showed two variants, a novel null variant (p.Trp548Ter) in the PDE6C gene causing COD type 4 (Achromatopsia) and a previously reported variant (p.Ile84Thr) in the PDZD7 gene causing NSHL. Both variants were found in the cis configuration on chromosome 10 with a genetic distance of about 8.3 cM, leading to their co-inheritance. However, two diseases could appear independently in subsequent generations due to crossover during meiosis.ConclusionsHere, we could successfully determine the etiology of a seemingly complex phenotype in two adjacent genes. We identified a novel variant in the PDE6C gene, related to achromatopsia. Interestingly, this variant could cooperatively cause visual disorders: cone dystrophy and cone-rod dystrophy.

DEVELOPMENT OF A NOVEL REVERSED-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR THE DETERMINATION OF SODIUM DITHIONITE IN BREAD PRODUCTS

Bread is a valuable food in Iranian families that is used as a source of energy, protein, minerals, and vitamins. Unfortunately, most bakeries process bread artificially to speed up the production process and inevitably resort to the use of harmful chemicals such as baking soda, and SDT (sodium hydrosulfite). In this study, the types of bread produced in Ilam City in terms of unauthorized use of SDT were measured. The research site is all active bakeries in Ilam city. Statistical analysis between different groups were determined using t-tests and ANOVA (SPSS-18). Data were expressed as mean ± SD. For all tests, Р values of less than 0.05 were considered significant. Each test was repeated three times. In this study, 80 bakeries were surveyed, of which 22 bakeries (27.5 %) were Lavash, 26 bakeries (32.5 %) were Barbari and 32 bakeries (40 %) were Sangak. The average SDT consumption in all bakeries was 20.62 and 36.3 %. The amount of SDT consumption was significantly higher in Lavash bread than in Barbari and Sangak bread. The lowest SDT consumption was reported in Sangak. The results showed that 95.5 % of Lavash bakeries did not meet the national standards in the use of SDT and this amount was reported 73.1 % and 34.4 % of Barbary and Sangak bakeries, respectively. In Lavash bakeries 4.5 %, Barbari 26.9 and Sangak 65.6 %, the SDT consumption was significantly in line with national standards (56.3 %). The results showed that the use of SDT has been done with different amounts depending on the type of bread in bakeries in Ilam city so the most use is related to Lavash bread and then Barbari and Sangak.

Association of Household Food Insecurity with Stunting and Underweight Among Iranian Children Aged 2 - 5 Years old

Background: Although previous literature has assessed the association of household food insecurity with nutritional outcomes among children, the findings are inconsistent across different study populations. Objectives: We aimed to evaluate the association of household food insecurity with nutritional outcomes among children residing in Khalkhal city, Iran. Methods: The present cross-sectional study was conducted on 300 Iranian children aged 2 - 5 years who visited urban and rural health care centers between November 2021 and March 2022. Subjects were included in the survey using multi-stage cluster sampling. Household food security status was assessed using the United States Department of Agriculture (USDA) 18-item food security questionnaire. Odds ratios (95% confidence interval) for stunting according to the food insecurity score were estimated using multivariable logistic regression in three models. Results: In the present study, 39% of participants had food security, while the prevalence of food insecurity without hunger, food insecurity with moderate hunger, and food insecurity with severe hunger were 22.3%, 23%, and 15.7%, respectively. In all models, both categorized and continuous food insecurity scores correlated negatively with weight (P for all < 0.001). Food insecurity did not predict the risk of stunting in all subjects before and after adjustment (Model 1: OR (CI) = 1.008 (0.96-1.05), P = 0.72; Model 2: OR (CI) = 1.01 (0.96 - 1.05), P = 0.65; Model 3: OR (CI) = 0.98 (0.92-1.04), P = 0.53). Conclusions: In the current study, we found that Iranian families with the lowest income had the highest food insecurity scores. Household food insecurity was negatively correlated with weight status among children aged 2 - 5 years.

“She is finally home”: feminist storytelling, family imaginaries and transnational solidarity in Irish abortion activism

ABSTRACT Across the so-called West, feminist storytelling positions reproductive justice and the often-twinned issue of women’s place within the family as a progressive issue. This conveniently ignores the inherent contradictions of the existence of only limited access to abortion in many Western nations, as well as parallel histories of access to reproductive justice in non-Western countries. Postcolonial Ireland, as an apparently Western country with a renowned history of anti-feminist legislation, has existed as one of these contradictions. In this article, we examine Irish feminists’ familial storytelling to reveal how they managed their contradictory position in a teleological narrative that positioned Western feminism as the epitome of progress. We adopt a comparative approach – looking at the lead up to the introduction of the Eighth Amendment of the Irish Constitution in 1983, which awarded the foetus constitutional rights, and then the high profile Repeal the 8th movement that successfully revoked that amendment in 2018 – to understand reproductive rights activists’ changing uses of “the family” to effect intergenerational and transnational solidarity. Applying Sara Ahmed’s concept of “sticky” emotions, we examine how feminists transformed “the Irish family” from a site of coldness and despair to one of hope, dignity, humanity and happiness.

SCAPER-Related Autosomal Recessive Retinitis Pigmentosa with Intellectual Disability: Confirming and Extending the Phenotypic Spectrum and Bioinformatics Analyses.

Mutations in the gene SCAPER (S phase Cyclin A-Associated Protein residing in the Endoplasmic Reticulum) have recently been associated with retinitis pigmentosa (RP) and intellectual disability (ID). In 2011, a possible involvement of SCAPER in human diseases was discovered for the first time due to the identification of a homozygous mutation causing ID in an Iranian family. Later, five studies were published in 2019 that described patients with autosomal recessive syndromic retinitis pigmentosa (arRP) accompanied by ID and attention-deficit/hyperactivity disorder (ADHD). This present study describes three patients from an Arab consanguineous family in Israel with similar clinical features of the SCAPER syndrome. In addition, new manifestations of ocular symptoms, nystagmus, glaucoma, and elevator palsy, were observed. Genetic testing of the patients and both parents via whole-exome sequencing revealed the homozygous mutation c.2023-2A>G in SCAPER. Phenotypic and genotypic descriptions for all available cases described in the literature including our current three cases (37 cases) were carried out, in addition to a bioinformatics analysis for all the genetic variants that was undertaken. Our study confirms and extends the clinical manifestations of SCAPER-related disorders.

The Farsi version of Caregiver Preparedness Scale in Iranian family caregivers of the older adults undergoing hemodialysis: a psychometric study

BackgroundEnhancing preparedness of family caregivers and support for caregiving is essential for the mutual benefit of both caregivers and the well-being of those under their care. This study aimed to translate and evaluate psychometric properties of the Caregiver Preparedness Scale among family caregivers of older adults undergoing hemodialysis.MethodsIn this methodological study, 400 family caregivers of older adult patients undergoing hemodialysis enrolled to the study via convenience sampling method. The study was conducted in two stages: translation and psychometric evaluation. At first, the translation of the scale was done using Beaton et al. method. In the psychometric evaluation stage, quantitative face validity, content validity, item analysis and construct validity of the scale were evaluated. The internal consistency of the scale was assessed through the calculation of Cronbach’s alpha, McDonald’s omega, and average inter-item correlation coefficients.ResultsAll items had an impact score greater than 1.5. The content validity ratio and the kappa coefficient for all items were above 0.75. In the item analysis, item 2, which had a correlation with the total score of less than 0.3, was removed. Following exploratory factor analysis, only one factor composed of all items (7 items) was extracted, explaining 75.7% of the total variance. This model had acceptable fit indices in confirmatory factor analysis. Cronbach’s alpha and omega of 0.95 and an average inter-item correlation of 0.75 were obtained.ConclusionsThe study results demonstrated that the Caregiver Preparedness Scale exhibits appropriate psychometric properties. Geriatric nurses can utilize this Scale for assessment of caregivers. This assessment can aid in decision-making regarding educational programs aimed at enhancing family caregiver preparedness.

Institutionalization of Sports for All in Iranian Families

Background: The institutionalization of sports in families plays a significant role in promoting the health of society. This study is aimed to extract effective background factors in institutionalizing sports in Iranian families. Methods: The present research follows an interpretive paradigm, inductive logic, and qualitative approach. Besides meta-synthesis approach and interviews were conducted. The research population of the present study included 166 national and international articles presented over the last twelve-year period. After screening the articles, 15 studies were finally selected which met the necessary criteria and were analyzed using the content analysis technique. In the next step, an interview was conducted with 23 experts in "public sports" in a targeted manner using the snowball and theoretical saturation techniques, and finally, the codes of the first and second stages were combined. Results: Meta-synthesis results led to the identification of 36 indices, the overlap of the codes was compared, and the results showed a reliability of 0.92 After the interview was conducted, 41 indices were identified. The comparison of the results in two time periods showed a reliability of 0.89. Finally, by latent content analysis, summarizing, overlapping, and merging the codes of the previous two steps, 47 influential indices affecting the institutionalization of sports in Iranian families were extracted. Conclusion: Based on the results of our research it can be concluded that by recognizing, planning, and creating mechanisms for the operationalization of the discovered factors, the process of institutionalizing physical activity in Iranian families will be facilitated.

Unveiling a Novel THOC2 Mutation's Role in X-linked Intellectual Disability

Background: Intellectual disabilities encompass a spectrum of neurodevelopmental disorders profoundly impacting an individual's cognitive abilities, adaptive behaviors, and communication skills. This article delves into the complex challenges encountered by an individual with intellectual disability, particularly examining the interplay between cognitive limitations and speech difficulties, while presenting a case report detailing the experience of a son within a non-consanguineous family diagnosed with intellectual disability due to a new genetic defect in THOC2, thereby contributing significantly to our comprehension of THOC2-related pathogenic variants. Case presentation: A 14-year-old boy from a non-consanguineous Iranian family presented with significant challenges in academics, communication, and adaptive skills, accompanied by speech problems and exhibiting distinctive physical characteristics. The exome-sequencing analysis revealed a novel hemizygous c.1559+5A>T mutation located in intron 14 (NM_001081550.2) within the THOC2 gene in the proband. Sanger sequencing further confirmed the mother as a carrier of the mutation, although she remains in good health, while the father exhibits a normal genotype. This delineates an X-linked inheritance pattern, shedding light on the familial transmission of the identified genetic anomaly. Conclusion: The precise identification of the c.1559+5A>T splicing mutation in the THOC2 gene, achieved through exome-sequencing, conclusively diagnoses X-linked intellectual disability in our patient. This breakthrough not only unravels the molecular intricacies contributing to intellectual disability but also underscores the urgency for accurate and swift disease diagnosis.

Joubert syndrome caused by a TMEM67 mutation: Genotype-phenotype analysis

Joubert syndrome (JS), a rare neurodevelopmental disorder, is characterized by a unique midbrain- hindbrain malformation known as the molar tooth sign, a distinctive radiological feature. Among the myriad manifestations associated with JS, the most prevalent features encompass hypotonia, ataxia, developmental delay, intellectual disability, abnormal eye movements, and neonatal breathing abnormalities. To date, 29 genes have been identified as contributors to the development of JS. This study aimed to pinpoint a pathogenic variant in JS within an Iranian consanguineous pedigree. We employed whole-exome sequencing (WES) to pinpoint a potential pathogenic variant likely responsible for the condition in an 8-year-old male patient. The WES analysis successfully revealed a novel homozygous missense mutation (c.725A>T; p.Asn242Ile) within exon 8 (NM_153704.6) of the TMEM67 gene. Subsequent validation through Sanger sequencing confirmed the presence of the chr8-93780603A>T mutation. This study elucidated JS within an Iranian family, uncovering a new TMEM67 gene mutation through comprehensive genetic analysis. The identification of this mutation enhances our understanding of the genetic landscape of JS, contributing valuable insights for both clinical diagnosis and future research endeavors.

Care burden and the predictive role of spiritual well-being and religious coping: A cross sectional study among Iranian family caregivers of patients with stroke.

The burden of care after a stroke is gaining recognition as a significant healthcare issue. Factors like religion and spirituality, encompassing religious coping and spiritual health, prove to be influential in anticipating the challenges faced by caregivers. The present study aimed to determine the relationship between care burden, spiritual health, and religious coping among caregivers of stroke patients. This cross-sectional research was conducted with the participation of 129 caregivers of stroke patients. The data was collected using the Ellison and Paloutzian spiritual well-being instruments, Pargament Religious Coping (RCOPE) brief version, and the Zarit burden interview (ZBI). Through a census, participants were recruited for the investigation. Data were analyzed using descriptive and inferential statistics (multivariate linear regression analysis). The study results indicate a strong and statistically significant relationship between the burden of caring and spiritual health (p < 0.001, β = 0.33). Furthermore, specific variables were identified as indicators of an increased burden of care, including positive religious coping (p = 0.04, β = 0.63), the familial relationship between the caregiver and patient, specifically as a child (p = 0.001, β = 29.26), and a sister (p < 0.001, β = 35.93). It is advisable to consider adopting and implementing appropriate support measures for coping strategies rooted in religion and spirituality. So, it is recommended to enhance the provision of comprehensive support, including psychological and religious interventions. This can be achieved through the collaborative efforts of support groups comprising psychiatric nurses, psychiatrists, psychologists, and religious experts.

Caregivers' demands: caring atmosphere expected by cancer patients' caregivers-a qualitative content analysis.

Family caregivers play a critical role in providing care for patients with cancer. However, the quality of their caregiving can be greatly impacted if the demands and expectations they experience are not identified. Therefore, this study aimed to explore the demands and perceived expectations of caregivers while caring for cancer patients. This qualitative study was conducted from June 2022 to September 2023. Face-to-face and in-depth semi-structured interviews were conducted to collect the experiences of 19 Iranian family caregivers of patients with cancer. Purposive sampling was used to select the participants. The interviews were analyzed using conventional content analysis and the rigor of the study was ensured by employing Lincoln and Guba's criteria. Three main themes and six subthemes were identified through data analysis. The themes that emerged from the caregivers' experiences included the following: (1) ambiguity in the healthcare system, (2) need for empathetic communication, and (3) forgotten caregivers in the healthcare system. Caregivers often feel overlooked, resulting in unfulfilled needs and expectations. It is imperative to explore potential solutions that provide caregivers information, empathetic communication, and support. Nurses, as key members of the healthcare team, should play a significant role in addressing this problem.

#2412 Monoallelic NEK8-related polycystic kidney disease in an Irish ADPKD cohort

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD), commonly caused by pathogenic variants in PKD1 and PKD2 genes, leads to enlarged cystic kidneys and typically present in adulthood where ∼70% of affected patients progress to kidney failure by their 7th decade of life. Recently, new genes have been reported that appear to explain some of the previously unresolved ADPKD-like cases. An example is the NEK8 gene, where monoallelic variants are reported to cause early-onset ADPKD with progressive phenotype. We are reporting 4 Irish families with monoallelic NEK8 variants. Method In-depth clinical and radiological evaluations were conducted on 250 families with polycystic kidney disease referred to the Irish Kidney Gene Project. All patients underwent genomic testing using gene-panel and exome Next Generation Sequencing (NGS), while multiple ligation probe amplification analysis of PKD1 or PKD2 was utilized in genetically unresolved families. The American College of Medical Genetics and Genomics guidelines were applied to assess variant pathogenicity. Results To date, 471 individuals representing 250 distinct families (F) have been studied, including 105 (42%) families with two or more individuals (326 individuals). 55.2% have reached end-stage kidney failure, with an average age of 49.1 ± 14.3 years. We identified pathogenic / likely pathogenic variants in 76% (190/250) of families, with variants in PKD1 accounting for 76.8% (146/190) and PKD2 accounting for 15.3% (29/190) of families, respectively. In familial cases with non-PKD1/PKD2 variants, we identified pathogenic variants in a small proportion of families with ADPKD-like phenotypes: IFT140 variants (n = 4), ALG5 (n = 2), 17q12 microdeletion (n = 2) and DNAJB11, ALG8, and ALG9 variants (n = 1 each). Upon thorough review of all genetically unresolved PKD families, 4 (6.7%) families were identified with monoallelic protein-kinase domain NEK8 variants [NM_178170.3]: p.R45W (in 2 families) and two other missense variants: p.N69D and p.R140L, none of which contained a second NEK8 variant despite extensive analysis. Autosomal dominant segregation was confirmed in two parent-child pairs, whereas the remaining two index patients reported no family history of kidney disease. The median age at the initial presentation was 12 years (IQR: 2.5–27.3), with a median follow-up period of 22.5 years at the last evaluation. The phenotype of all patients was consistent with polycystic kidney disease with the absence of liver and pancreatic cysts. All patients were diagnosed with hypertension at an average age of 15.3 ± 12.2 years. Cerebral aneurysms were detected in two patients (F1: at age 61 years and F4: at age 54 years), while F3 was reported to have childhood-onset frontal bossing, prominence cerebrospinal fluid, and large arachnoid cysts. Approximately 67% [4/6] patients progressed to end-stage kidney failure by the 3rd decade of life. Compared to families with PKD1/PKD2 variants, families with NEK8 variants were characterized by earlier average age at initial presentation (14.5 versus 29.9 years; p 0.01) and progression to end-stage kidney failure (15.5 versus 49.6 years; p &amp;lt; 0.0001). Table 1 summarizes the clinical and genetic characteristics of the reported families. Conclusion We provide further evidence that monoallelic NEK8 variants cause early presentation and progressive ADPKD-like phenotype. Sequencing for monoallelic NEK8 variants in patients with childhood and early-adulthood cystic kidney disease can inform renal prognosis, treatment planning, familial screening and reproductive choices.

Identification of novel and known genetic variants associated with hereditary hearing loss in iranian families using whole exome sequencing.

Hearing loss (HL) is a common sensory impairment worldwide, with genetic and environmental factors contributing to its occurrence. Next Generation Sequencing (NGS) plays a crucial role in identifying the genetic factors involved in this heterogeneous disorder. In this study, a total of 9 unrelated Iranian families, each having at least one affected individual who tested negative for mutations in GJB2, underwent screening using whole exome sequencing (WES). The pathogenicity and novelty of the identified variant was checked using various databases. Co-segregation study was also performed to confirm the presence of the candidate variants in parents. Plus, The pathogenicity of the detected variant was assessed through in silico analysis using a number of mutation prediction software tools. Among the 9 investigated families, hearing loss-causing genes were identified in 6 families. the mutations were observed in USH2A, CLRN1, BSND, SLC26A4, and MITF, with two of the identified mutations being novel. Discovering additional variants and broadening the range of mutations associated with hearing impairment has the potential to enhance the diagnostic effectiveness of molecular testing in patient screening, and can also lead to improved counseling aimed at reducing the risk of affected offspring for high-risk couples.

The Experiences of Family Caregivers After Losing a Patient with Advanced Cancer: A Qualitative Study

Background: In patients with advanced cancer, family caregivers are crucial in providing care throughout the illness, particularly towards the end of life. These caregivers often face unique challenges and emotions that may differ significantly from those experienced by other family members following the patient’s death. Objectives: The purpose of this study was to explore the experiences of family caregivers following the loss of a patient with advanced cancer. Methods: A qualitative study was conducted in Iran from June 2023 to January 2024 to explore the experiences of family caregivers after the death of a patient with advanced cancer. Using purposive sampling, face-to-face, in-depth semi-structured interviews were carried out with 14 Iranian family caregivers of cancer patients. The interviews were subjected to conventional content analysis for thematic extraction. To ensure the trustworthiness and rigor of the study, Lincoln and Guba's criteria were applied. Results: Data analysis and abstraction resulted in the formation of three main categories with eight sub-categories. The categories extracted from the caregivers' experiences were: Caregiver's inconsolable mourning, Unforgettable experience of caring for loved ones, and Constant mind involvements. Conclusions: The different experiences of family caregivers after the death of a patient and the more intense emotions they experience indicate that caregivers require additional attention and support following the loss. Consequently, health systems should identify these individuals during the patient care process and provide targeted support after the patient's death.

Detection of a novel pathogenic variant in KCNH2 associated with long QT syndrome 2 using whole exome sequencing

BackgroundLong QT syndrome (LQTS) is a cardiac channelopathy characterized by impaired myocardial repolarization that predisposes to life-threatening arrhythmias. This study aimed to elucidate the genetic basis of LQTS in an affected Iranian family using whole exome sequencing (WES).MethodsA 37-year-old woman with a personal and family history of sudden cardiac arrest and LQTS was referred for genetic study after losing her teenage daughter due to sudden cardiac death (SCD). WES was performed and variants were filtered and prioritized based on quality, allele frequency, pathogenicity predictions, and conservation scores. Sanger sequencing confirmed segregation in the family.ResultsWES identified a novel heterozygous frameshift variant (NM_000238.4:c.3257_3258insG; pGly1087Trpfs*32) in the KCNH2 encoding the α-subunit of the rapid delayed rectifier potassium channel responsible for cardiac repolarization. This variant, predicted to cause a truncated protein, is located in the C-terminal region of the channel and was classified as likely pathogenic based on ACMG guidelines. The variant was absent in population databases and unaffected family members.ConclusionThis study reports a novel KCNH2 frameshift variant in an Iranian family with LQTS, expanding the spectrum of disease-causing variants in this gene. Our findings highlight the importance of the C-terminal region in KCNH2 for proper channel function and the utility of WES in identifying rare variants in genetically heterogeneous disorders like LQTS. Functional characterization of this variant is warranted to fully elucidate its pathogenic mechanisms and inform personalized management strategies.