Iranian Family Research Articles

A novel missense pathogenic variants of TMEM53 in an Iranian family with craniotubular dysplasia, Ikegawa type.

Craniotubular dysplasia, Ikegawa type (CTDI) is a rare autosomal recessive skeletal dysplasia characterized by hyperostosis of the calvaria and skull base, metadiaphyseal undermodeling of the long tubular bones, and mild shortening and diaphyseal broadening of the short tubular bones. Its causal gene is TMEM53. Six CTDI families have been reported; however, its clinical course and prognosis still remain to be determined. Here, we report two Iranian siblings carrying a novel homozygous missense variant of TMEM53. The affected individuals were referred for progressive severe visual loss of unknown cause. The patient had severe optic atrophy and optic canal narrowing. Radiographic evaluation suggested the diagnosis of CTDI, which was confirmed by the identification of TMEM53 variant (c.704G > T, p.R235L) co-segregating in the consanguineous family. The proband underwent trans-nasal endoscopic optic canal decompression and showed remarkable improvement in visual acuity and daily visual tasks. We recommend early comprehensive clinical and genetic evaluation followed by proper treatment to improve the prognosis of CTDI.

Genetic etiology of Perrault syndrome in Iranian families: first report from Iran and literature review.

Perrault syndrome (PS) is an extremely rare autosomal recessive condition characterized primarily by bilateral sensorineural hearing loss in both genders and primary or secondary ovarian failure in females. Neurological features such as cerebral ataxia, peripheral neuropathy, epilepsy, and intellectual disability are frequent manifestations of PS. To date, six genes have been reported to cause PS, and nearly 100 families have been identified worldwide with this syndrome. Exome sequencing was performed on two unrelated Iranian families presenting with Perrault syndrome. Family A included three offspring affected with bilateral severe to profound congenital hearing loss, cerebral ataxia, epilepsy, and intellectual disability. Family B included a female affected with bilateral moderate to severe hearing loss and peripheral neuropathy. In Family A, a compound heterozygous mutation (c.21delA and a novel missense mutation c.512C > G) in the CLPP gene was identified. In Family B, a homozygous mutation c.874C > A in the TWNK gene was found in the affected female. These findings represent the first report of genetic variations in the CLPP and TWNK genes in Iranian families with Perrault syndrome. The study expands the genetic landscape of Perrault syndrome by identifying novel mutations in the CLPP and TWNK genes. It also highlights the utility of exome sequencing as a cost-effective and powerful tool for diagnosing rare and complex genetic disorders like Perrault syndrome.

Improved Diagnostic Yield in Recessive Intellectual Disability Utilizing Systematic Whole Exome Sequencing Data Reanalysis

ABSTRACTRecent advances in next generation sequencing (NGS) have positioned whole exome sequencing (WES) as an efficient first‐tier method in genetic diagnosis. However, despite the diagnostic yield of 35%–50% in intellectual disability (ID) many patients still remain undiagnosed due to inherent limitations and bioinformatic short‐comings. In this study, we reanalyzed WES data from 159 Iranian families showing recessively inherited ID. The reanalysis was conducted with an initial clinical re‐evaluation of the patients and their families, followed by data reanalysis using two updated bioinformatic pipelines. In the first phase, the BWA‐GATK pipeline was utilized for alignment and variant calling, with subsequent variant annotation by the ANNOVAR tool. This approach yielded causative variants in 17 families (10.6%). Among these, six genes (MAZ, ACTR5, AKTIP, MIX23, SERPINB12, and CDC25B) were identified as novel candidates potentially associated with ID, supported by bioinformatics functional annotation and segregation analysis. In the second phase, families with negative results were reassessed using the Illumina DRAGEN Bio‐IT platform for variant‐calling, and Ilyome, a newly developed web‐based tool, for annotation. The second phase identified likely pathogenic variants in two additional families, increasing the total diagnostic yield to 11.9% which is consistent with other studies conducted on cohorts of patients with ID. In conclusion, identification of co‐segregating variants in six novel candidate genes in this study, emphasizes once more on the potential of WES reanalysis to uncover previously unknown gene‐disease associations. Notably, it demonstrates that systematic reanalysis of WES data using updated bioinformatic tools and a thorough review of the literature for new gene‐disease associations while performing phenotypic re‐evaluation, can improve diagnostic outcome of WES in recessively inherited ID. Consequently, if performed within a 1–3 year period, it can reduce the number of cases that may require other costly diagnostic methods such as whole genome sequencing.

A Novel Candidate Gene MACF1 is Associated with Autosomal Dominant Non-syndromic Hearing Loss in an Iranian Family

Cytoskeletal dynamics, the interplay of actin, microtubules, and septins, is a highly coordinated and tightly regulated process. Defects in the proteins involved can result in a wide range of cellular consequences. Hearing loss is the most common sensory defect and exhibits extraordinary genetic and phenotypic heterogeneity. Currently, there are more than 170 genes casually linked to non-syndromic hearing loss (NSHL), of which more than 60 are associated with autosomal dominant inheritance. Here, we add to this growing number by implicating MACF1 (OMIM # 608271), as a novel candidate gene for autosomal dominant non-syndromic hearing loss (ADNSHL). MACF1’s cytoskeleton integrator function and hair cell expression pattern lead one to believe that it is a necessary protein for hair cells. Many protein domains in MACF1 allow for dynamic interaction with the cytoskeleton. A large Iranian family segregating progressive ADNSHL was recruited for this study. The proband had bilateral mild-moderate sensorineural hearing loss and was negative for GJB2 mutations. After applying exome sequencing on the proband, a missense mutation c.1378C>T (p.His460Tyr) was found in MACF1 and co-segregated with the hearing loss in the extended family. We speculated that MACF1 mutations probably cause non-syndromic hearing loss inherited in an autosomal dominant manner. The potential functional impact of the identified variant will be investigated through further analysis.

The Effect of an Educational Program Based on Behavioral Intention Model on Childbearing in Women During the Covid 19 Pandemic

Background: Currently, fertility and childbearing rates in Iran are below the replacement level (1.2 children), and Iranian families have a low propensity to have children. The COVID-19 pandemic will also have a negative impact on the decision of couples to have children. The present study was conducted with the aim of investigating the effectiveness of an educational program on women’s childbearing intention under the conditions of the COVID-19 pandemic. Materials and Methods: This study was a clinical trial with a pretest–posttest design, conducted on 80 women (control group = 40 and intervention group = 40) in comprehensive health centers in 2019. The educational program was delivered to the intervention group in 3 sessions. The data collection tools included the Attitudes to Fertility and Childbearing Scale (AFCS), Demographic Information Questionnaire, and researcher-made fertility intention questionnaire. Data were analyzed using t-test, Mann–Whitney, Chi-square test, ANOVA, Bonferroni post hoc test, and Wilcoxon test. Results: The women in the intervention group were in the age range of 18 to 44 years and in the control group were in the age range of 19 to 44 years. The results showed that the mean scores of attitude toward fertility and intention to have children after training were significantly different between the two groups. However, after the training, it was significantly higher in the intervention group than in the control group (F1,67 = 1037, p < 0.001). Conclusions: It seems that the implementation of the use of theoretical models can be effective in the informed decision of families, especially women, for childbearing.

Ataxia With Vitamin E Deficiency: Case Series, Vitamin E Therapy Response, Founder Effect, and In Silico Analysis.

Ataxia with Vitamin E Deficiency (AVED) is a rare autosomal recessive genetic disorder, that caused by pathogenic variants in the TTPA gene, which encodes the alpha-tocopherol transfer protein. This study investigates eight patients from three consanguineous Iranian families, using exome sequencing (ES) and Sanger sequencing to identify novel pathogenic variants in the TTPA gene. Two variants were identified: c.219T>A (p.Tyr73*) and c.205-1G>C. the first one (c.219T>A) related to potentially founder effects within regions of homozygosity. Clinical outcomes varied among patients based on vitamin E therapy initiation, with early treatment preventing severe neurological impairment. These findings improve knowledge of TTPA variants, supporting targeted genetic-based therapy. This study emphasizes the importance of genetic screening in consanguineous communities for the early detection and management of Mendelian diseases, with additional implications for managing rare genetic disorders generally.

Language ideologies guiding language practices and management strategies: a study of family language policy among Iranian families in The Netherlands

ABSTRACT This study seeks to explore the Family language policy (FLP) of Iranian migrant families in the Netherlands, with a particular focus on those who preserve and use Persian as their heritage language. Drawing on [Spolsky, B. 2004. Language Policy. Cambridge: Cambridge University Press.] tripartite language policy model, the study looks into the language ideologies, language practices, and language management strategies adopted by nine families, who were recruited through snowball sampling. Semi-structured interviews were used to compile the data. The findings indicate that the home sphere plays a pivotal role in the continued use of Persian. As for parental language ideologies, all respondents shared a longing to uphold Persian and cited an array of cultural, emotional, practical, and cognitive reasons for embracing Persian as their heritage language. The studied parents reported that Persian is the constant choice of communication within their households and employed deliberate strategies to ensure the sustainability of Persian within the home setting. The findings of this study bear important implications for understanding the dynamics of language maintenance within the Iranian diaspora and contribute to the scholarly discourse on FLP and heritage language maintenance.

Galloway-mowat syndrome 3 (GAMOS3): a novel disease-causing variant in OSGEP gene and expansion of the clinical spectrum.

Galloway-Mowat syndrome type 3 (GAMOS3) is a rare genetic disorder with renal and neurological complications caused by pathogenic variants in the OSGEP gene. Here, we report the molecular basis and clinical features in an Iranian family. Our proband, a 10-month-old female patient, presented with microcephaly, global developmental delay, lower limb spasticity, facial dysmorphisms, and renal tubulopathy. Brain magnetic resonance imaging (MRI), electroencephalography (EEG), and laboratory tests were performed to evaluate the clinical features. WES, Sanger sequencing, computational variant analysis, and gene expression analysis were conducted to identify, validate, and evaluate the genetic cause. Additionally, I-TASSER, HADDOCK, and GROMACS tools were utilized for protein modeling, computational docking, and molecular dynamics simulation (MDS), respectively. Blood and urine tests revealed proteinuria, hypercalciuria, and hypoalbuminemia. Brain MRI detected craniosynostosis, global parenchymal atrophy, and dysgenesis of the corpus callosum. Exome sequencing identified a previously unreported homozygous variant (NM_017807.4, c.689 G > T/p.C230F) in OSGEP, demonstrating co-segregation with the condition in the family. This missense variant did not significantly change the mRNA transcription. In-silico experiments predicted that this variant would likely alter the protein's structure and impair its normal functioning. Molecular docking results indicated that this variant significantly affects the protein interactions between OSGEP and LAGE3 proteins. Furthermore, MDS findings demonstrated that the p.C230F variant induced a conformational change in the mutant structure, potentially modifying its flexibility and stability. Identification of this variant contributes to expanding the OSGEP gene variant database, establishing a solid scientific foundation for precise clinical diagnosis and treatment.

Clinical and genetic diversity in Iranian individuals with RAPSN-related congenital myasthenic syndrome.

Congenital myasthenic syndromes (CMSs) are genetic disorders affecting motor function with variable symptoms. RAPSN-related CMS, caused by mutations in the RAPSN gene, leads to muscle weakness. Accurate diagnosis is essential for proper management. This study aims to analyze six Iranian families affected by RAPSN-CMS, focusing on clinical manifestations, genetic variants, treatment response, and outcomes. Clinical assessments, genetic analysis, and whole-exome sequencing were performed on the six families to identify RAPSN gene mutations. The study examined symptoms, disease severity, age of onset, treatment response, and outcomes. Treatment with pyridostigmine and salbutamol was given to assess its effectiveness. Three homozygous known variants in RAPSN gene were identified: c.491G > A in three families, c.264C > A in two families, and c.-210A > G in one family. Clinical assessments showed diversity in symptoms and treatment responses. Pyridostigmine and salbutamol treatment improved symptoms and quality of life. This study highlights the significance of molecular diagnosis for RAPSN-related congenital myasthenic syndromes (CMS) in Iran, marking the first comprehensive genetic analysis in the region. The identification of specific pathogenic variants underscores the unique genetic landscape of local patients. Furthermore, our long-term follow-up revealed variable treatment responses, emphasizing the need for personalized care strategies. The clinical variability among patients with identical mutations necessitates a multidisciplinary approach for effective management. By enhancing genetic awareness and refining follow-up methods, we aim to improve diagnosis accuracy and interventions, fostering better outcomes for affected families in the Iranian population.

Introducing a novel TRAPPC10 gene variant as a potential cause of developmental delay and intellectual disability in an Iranian family.

TRAPP complexes are crucial components for intracellular transport and cellular organization. Their role in vesicle trafficking, particularly through their involvement in the secretory pathway, make them more important in neurodevelopmental mechanisms. This study aims to identify a novel genetic variant, associated with developmental delay and intellectual disability by analyzing a consanguineous Iranian family. Here, we performed whole-exome sequencing on an Iranian family, originating from a small population. The patient presented with severe developmental delay, microcephaly, and behavioral abnormalities. Through our analysis, we discovered a new biallelic variant on a previously introduced gene: TRAPPC10 (NM_003274.5): c.3222C > A; p.(Cys1074Ter) that is a potential cause for these specific clinical characteristics. Previous functional analysis suggest that the mutation causes premature termination of protein translation, likely leading to nonsense-mediated decay because of biallelic loss of functional TRAPPC10 protein which leads to severe developmental delay, microcephaly, and behavioral abnormalities such as aggression and autistic traits. The aim of this research is to discover a novel variant in the TRAPPC10 gene that is responsible for a particular neurodevelopmental condition, dominantly characterized by developmental delay, intellectual disability, and microcephaly. These findings advance the comprehension of TRAPP-related diseases and emphasize the need for further exploration into the impact of TRAPPC10 on the development of the nervous system.

Exploring the Molecular Interaction Between NR2E3 and NR1D1 in Retinitis Pigmentosa: A Docking and Molecular Dynamics Study.

Retinitis pigmentosa (RP) is a hereditary retinal disorder that gradually leads to vision loss due to photoreceptor cell degeneration. This study aims to investigate the clinical features and genetic underpinnings of RP within a large Iranian family. Our focus centered on mutations in the NR2E3 gene, which plays a critical role in the development and maintenance of the retina. Twenty-five family members showed symptoms of RP, and fourteen of them underwent clinical examinations conducted by geneticists and ophthalmologists. The DNA samples of five individuals diagnosed with RP from the family were subjected to whole-exome sequencing (WES) as part of the study. The candidate variant identified through WES was subsequently confirmed using bidirectional sequencing in additional family members. Additionally, in silico analysis, including molecular modeling, protein-protein docking, and molecular dynamics simulation (MD), was employed to assess potential pathogenic effects associated with the candidate variants. Ophthalmic examination revealed night blindness, which is a common symptom among affected individuals. Genetic analysis identified a homozygous missense variant (c.934G>A/p.R311Q) in NR2E3 exon 6, which co-segregates with other affected family members. Furthermore, molecular docking analysis indicated potential disruption in the binding affinity between NR2E3 and NR1D1 proteins. In-depth, molecular dynamics analysis, considering parameters such as RMSD, RMSF, and hydrogen bonding, revealed notable differences between normal and mutant protein complexes. Exploring the molecular interaction between NR2E3 and NR1D1 provides new insights into the pathogenic mechanism of the p.R311Q mutation in RP.

Exploring the ethical decision-making experience of caregivers of end stage cancer patients in Iran: a phenomenological study

BackgroundEthical decision making is a complex issue because it strongly depends on the religion, beliefs, traditional laws and moral views of each society. The purpose of this study was to explore the experience of Iranian family caregivers of end stage cancer patients about ethical decision making.MethodsThis qualitative study is based on van Manen’s method of hermeneutic phenomenology. In-depth interviews were carried out to collect data. Participants were 12 caregiver. Audiotapes were transcribed and analyzed for common themes that represented the participants’ experiences. Trustworthiness of the findings was established using the Lincoln and Guba’s criteria.ResultsThree themes reflected the essence of caregivers’ lived experience including; fluctuating between hope and despair, wandering dilemma, and ethical decision making. Each of these themes consisted of several subthemes.ConclusionThe present study revealed that, the caregivers of terminally ill cancer patients need different information about prognosis and end of life decision making process. Our perception of how families negotiate ethical issues in their decision-making is still developing. Opportunities should be created to empowering caregivers to talk about their uncertainties and concerns.

Validation of Gottman's "Success and Failure in Marriage" Questionnaire based on the Multivariate Item-Response Theory

Aim: The success and failure of marriage plays a fundamental role in well- being of society and individuals. Therefore, it is highly desirable to have a method to evaluate and predict the future of a marriage. As such, the aim of the present study is to validate Gottman's (2012) “success and failure in marriage questionnaires”. Methods: This is a cross-sectional study and the research design used a descriptive-correlation and test validation. Modern method of multivariate item-response theory was used for data analysis. The questionnaires used in this research were for validation, criticism, contempt, defensiveness, stonewalling, and attitude about Gottman’s past (1401). Results: In this study, the best model for factor analysis was determined to be the item-response multivariate factor analysis method and with the aid of this model, two dimensions were reported for the Gottman questionnaires. Also, the items factor loadings, the parameters of the Item-response theory and the analysis of the Items were reported. Conclusion: At the end, two dimensions of "fight mode" and "positive and negative emotions towards marriage and spouse" were identified for these questionnaires. Data analysis showed that Gottman's questionnaires have good validity in Iranian families and can be used in clinical, research and organizational environments and it is suitable to assess Iranian families. Also, the data in this research showed that Gottman's theory has good empirical support, regardless of the cultural context.

Factors influencing the ability of family caregivers of Alzheimer’s patients within Iranian families to continue and persist in their caregiving roles: a qualitative study

BackgroundUnderstanding the motivations driving family members to continue caring for individuals with Alzheimer’s disease is crucial for enhancing social support programs within community health systems. This study specifically explores the factors influencing Iranian family caregivers’ ability to persist in their caregiving roles.MethodsThis qualitative study was conducted using conventional content analysis with 22 participants in 2022 in Babol (a city in northern Iran). The inclusion criteria for the study included caregivers of Alzheimer’s patients who had been the primary caregivers for at least one year for patients with a confirmed diagnosis of Alzheimer’s disease. The sampling method was purposive, ensuring maximum variation in social position, demographic status, and stages of Alzheimer’s disease after the onset of symptoms. In this research, data were collected from caregivers of Alzheimer’s patients through semi-structured interviews and in-depth individual interviews. The data were analyzed using MAXQDA software.ResultsOne category and four subcategories were identified to explain the continuity of the caring role in family caregivers of Alzheimer’s patients. The category was “on the Fence of the Caring Role.” The subcategories included Commitment to Care (Being Determined, Being Indebted, Feeling Dutiful), Coercion to Care (Giving in to the Caring Role Due to Family Requirements, Patient Care Due to Financial Problems), Socio-Cultural Beliefs and Concerns (Spiritual and Religious Tendencies, Social Stigma and Social Fears), and Attachment and Love for the Patient (Feeling Pity, Feeling Nostalgia for Kinship).ConclusionFamily caregivers are deeply engaged in their roles, often feeling trapped by various pressures. Recognizing these dimensions can inform policymakers and health practitioners in developing targeted interventions, such as respite care programs, financial support, and community resources, aimed at alleviating caregiver burden and enhancing the quality of care for patients. By addressing the complexities of the caregiver experience, effective strategies can be implemented to support both patients and their caregivers, ultimately improving health outcomes within the community.

The Homozygous Pathogenic CAPN3 Variant Identified Using Whole-exome Sequencing in Iranian Family With Limb-girdle Muscular Dystrophy Recessive 1

The Homozygous Pathogenic CAPN3 Variant Identified Using Whole-exome Sequencing in Iranian Family With Limb-girdle Muscular Dystrophy Recessive 1

A Frameshift Variant in ANKRD24 Implicates Its Role in Human Non-Syndromic Hearing Loss.

Hearing loss (HL) is the most prevalent sensorineural disorders, affecting about one in 1000 newborns. Over half of the cases are attributed to genetic factors; however, due to the extensive clinical and genetic heterogeneity, many cases remain without a conclusive genetic diagnosis. The advent of next-generation sequencing methodologies in recent years has greatly helped unravel the genetic etiology of HL by identifying numerous genes and causative variants. Despite this, much remains to be uncovered about the genetic basis of sensorineural hearing loss (SNHL). Here, we report an Iranian consanguineous family with postlingual, moderate-to-severe autosomal recessive SNHL. After first excluding plausible variants in known deafness-causing genes using whole exome sequencing, we reanalyzed the data, using a gene/variant prioritization pipeline established for novel gene discovery for HL. This approach identified a novel homozygous frameshift variant c.1934_1937del; (p.Thr645Lysfs*52) in ANKRD24, which segregated with the HL phenotype in the family. Recently, ANKRD24 has been shown to be a pivotal constituent of the stereocilia rootlet in cochlea hair cells and interacts with TRIOBP, a protein already implicated in human deafness. Our data implicate for the first time, ANKRD24 in human nonsyndromic HL (NSHL) and expands the genetic spectrum of HL.

Retraction: Novel splicing variant c. 208+2T>C in BBS5 segregates with Bardet-Biedl syndrome in an Iranian family by targeted exome sequencing.

Retraction: Novel splicing variant c. 208+2T>C in BBS5 segregates with Bardet-Biedl syndrome in an Iranian family by targeted exome sequencing.

Different Forms of Violence in Farībā Vafī’s Writing: The Case of The Secret in the Alleys and The Grimace

Abstract Readers frequently come across signs—both hidden and manifest—of violence perpetrated against women in Farībā Vafī’s novels. Vafī’s work is characterized by narrative heterogeneity as well as a multivarious vocabulary that is both ironic and sardonic. Her writing is situated within the volatile domesticity of “normal” Iranian families. In this setting, she describes the encounter, contrast, and melding between tradition and modernity in the broadest sense and different generations of women. This article examines how the author portrays violence against women in her writing, analyzing both the psychological and sociological factors that contribute to this depiction.

‘The voice of the child? The child has no voice’: an Irish study exploring the voice of young children in decisions regarding contact

Since January 2016, Irish family law courts have been obliged to take into consideration the voices of children in proceedings where decisions regarding contact with parents are being made. This article examines the findings of an Irish study that shed light on how young children’s voices are heard in decisions regarding contact with parents who do not, or no longer, live together. The views of key stakeholders who have some involvement with contact arrangements for young children in the 0–6 years age category are highlighted. A thematic analysis of the data was conducted in order to understand various perspectives on how and under what circumstances young children are heard in contact cases. The findings demonstrate that the voices of young children are virtually absent in family law decisions regarding contact. Determining factors relate to the infrastructure of the courts, a significant lack of resources to support the Irish family law system and significant variation in practice approaches between social and legal professionals. As a result of these findings, suggestions are proposed for informing practice and improving service delivery in family law in a way that best meets the needs and rights of young children.

"Doing Housework with a Walker? No Way!": Exploring the Perceptions of Community-Dwelling Frail Older Adults and Their Informal Caregivers on "Informal Caregiver-Induced Forced Immobility".

Family caregivers should focus on maintaining independence when assisting older adults with mobility. This may, however, bring about a counterproductive effect, namely Informal Caregiver-induced Forced Immobility (ICFI). This study explored the perceptions and experiences of older adults and their informal caregivers regarding ICFI. This qualitative study used a conventional content analysis approach and was conducted from January to September 2023 in Tabriz, Iran. Twenty older adults (aged 60 years and above) who had used a mobility aid, such as a cane or walker, and 14 informal caregivers were purposefully (purposive sampling) selected to participate in the study. Individual semi-structured interviews were conducted until data saturation was achieved. MAXQDA ver. 20.0 software (VERBI Software, Germany) was used to manage and analyze the data. Based on the participants' perceptions, ICFI means that for an older adult, "social interaction/social participation is limited," "performing activities of daily living is disallowed," and "engaging in physical activities and exercising is prohibited." Our findings revealed the concept of ICFI from various perspectives in Iranian families with older adults, leading to a clearer understanding of this phenomenon. This aspect should be considered when developing intervention strategies for the care of older adults in home and residential care settings by, health practitioners, gerontologists, and policymakers. This research can serve as a foundation for future studies to develop pertinent indicators and tools for measuring ICFI in the hope of providing sufficient evidence to support interventions that aim to prevent or stop ICFI.