Iranian Family Research Articles

Validation and Development of the Iranian Family Instability Scale based on the Lived Experience of Women Who Experienced Extramarital Relationship: A Mixed Method Study

Introduction: Various studies have cited several reasons for the instability of the Iranian family, but what was missing was a native scale for such studies. Therefore, this study aims to validate the Iranian family instability scale based on the lived experience of women who experienced extramarital relationships.
 Method: The present study utilized a mixed method. In the qualitative part of the study, semi-structured interviews were used to examine the lived experience of women who experienced extramarital relationships. The statistical population of the present study was women with extramarital affairs who referred to counseling centers in Yazd in 2020. By multi-stage cluster sampling, 540 subjects were selected. In this study, the marital adjustment and attitudes toward infidelity questionnaires were used.
 Results: Exploratory factor analysis, Cronbach's alpha method, concurrent validity, and confirmatory factor analysis were used to investigate the factors extracted from the interviews, the reliability, the validity of the scale, and also the fit of the research conceptual model, respectively.
 Conclusion: The results identify Iranian family instability factors in three levels and five subscales, including maternal role and religious myths, parenting knowledge, self-esteem and feelings of inferiority, relationship and aesthetic challenges, and apostasy and pre-relationship relationships. They are measured in a 35-question scale called "Iranian Family Instability Scale". The results of the present study show that the instrument of Iranian family instability has good validity and reliability and Cronbach's alpha of the whole scale is equal to 0.89.

Gnathodiaphyseal dysplasia with a novel genetic variant in a large family from Iran

BackgroundGnathodiaphyseal dysplasia (GDD) is an ultrarare autosomal dominant bone dysplasia characterized by cementoosseous lesions of the jawbones, bone fragility, frequent bone fractures at the young age, bowing of tubular bones, and diaphyseal sclerosis of long bones associated with generalized osteopenia. GDD is caused by point mutations in anoctamin‐5 (ANO5) on chromosome 11p14.3. For the past few years, next generation sequencing (NGS) technology has facilitated the discovery of causative variants in genetically heterogeneous diseases.MethodsIn this study, exome sequencing (ES) was performed using the DNA sample of the proband. Family histories and clinical information were collected through comprehensive medical examination and genetic counseling.ResultsES results identified a heterozygous variant, NM_213599.3:c.1078T>C(p.Cys360Arg) in the ANO5 gene. Sanger sequencing was performed to confirm the detected pathogenic variant in DNA samples of the entire family (except deceased individuals), which segregated with the disease within the family. Finally, in silico analysis was applied to test the pathogenicity of the variant using various online software.ConclusionIn summary, our investigation identified a novel pathogenic variant in the ANO5, responsible for gnathodiaphyseal dysplasia in a large Iranian family. Therefore, based on the present study, this variant can be helpful for diagnosis and effective management of GDD patients.

Hb Mazandaran (α1) α51 Gly > Cys(CE9), c.154 GGC > TGC: A Novel Haemoglobin Variant of α1-Globin Gene

This is a report of a novel variant of the α1-globin gene—(α1) α51 Gly > Cys (CE9), c.154 GGC > TGC, named Hb Mazandaran, which was observed in an Iranian family. This variant gives rise to a previously undescribed haemoglobin variant that was undetectable by capillary haemoglobin electrophoresis (CE). This variant was detected in two cases in combination with β-globin mutation, and it does not seem to be associated with severe haematological abnormalities in the carriers.

Genotypic and phenotypic spectrum of Myofibrillar Myopathy 7 as a result of Kyphoscoliosis Peptidase deficiency: The first description of a missense mutation in KY and literature review

KY is located on chromosome 3 and encodes a transglutaminase-like protein in the skeletal muscles, namely Kyphoscoliosis Peptidase. KY is primarily involved in the formation and stabilization of neuromuscular intersections making it essential for the development of the musculoskeletal system. Mutations in KY cause Myofibrillar Myopathy-7 (MFM-7) and Hereditary Spastic Paraplegia (HSP). MFM-7 is an early onset muscle disorder with an autosomal recessive inheritance marked by progressive muscle weakness and joint contractures. Herein, we describe an Iranian family with MFM-7 caused by a homozygous novel variant in KY. We identified a homozygous variant (NM_178554.6:c.1247T > A, p. Ile416Asn) in KY in two patients born to consanguineous parents and the same heterozygous mutation in their parent by Whole-Exome Sequencing. The patients manifest muscle weakness, muscle atrophy, mobility restriction, and hyporeflexia. Lastly, we reviewed the phenotype and corresponding genotype of the previously reported cases with pathogenic variants in KY.

The Clinical and Molecular Assessment of Iranian Families with Severe Congenital Neutropenia, Identification of HYOU1 and SHOC2 as Potential Novel Gene Defects.

Neutropenia congenita grave (SCN) is a rare disease with a genetically and clinically heterogeneous nature, usually diagnosed in childhood, with an elevated risk of infections such as otitis, skin infections, pneumonia, deep abscesses, and septicemia. Patients with SCN also have an increased risk of leukemia, and mutations in the ELANE and the HAX1 genes have been observed in those patients. This study was conducted to genetically screen six Iranian families with SCN who have at least one affected person. In the first step, all exons and intron boundaries of ELANE and HAX1 genes were sequenced in probands. Cases with no pathogenic mutations were tested through whole-exome sequencing (WES). Analysis showed five different variants in ELANE (c.377 C>T), HAX1 (c.130_131 insA), HYOU1 (c.69 G>C and c.2744 G>A) and SHOC2 (c.4 A>G) genes in four families. We found that two out of six families had mutations in ELANE and HAX1 genes. Moreover, we foundtwo novel mutations at the HYOU1 gene that had not previously been reported, as well as a pathogenic mutation at SHOC2 with multiple phenotypes, that will contribute to determining the genetic basis for SCN. Our study revealed that WES could help diagnose SCN, improve the classification of neutropenia, and rule out other immunodeficiencies such as autoimmune neutropenia, primary immunodeficiency diseases, and inherited bone marrow failure syndromes.

The effectiveness of structural family therapy in repairing behavioral problems and improving family functioning in single-parent families in Iran.

Family is foundational to Iranian culture and society and traditional families have been upheld by religious and political institutions since ancient times. However, the incidence of single-parent families in Iran is increasing and literature on treating dysfunction in these families in therapy is lacking. This study examines the effectiveness of structural family therapy (SFT) in addressing problems in family functioning and children's behavior in single-parent Iranian families using a single-case, multiple baseline, ABA design. Participants included five single mothers and their children who received SFT for 8 weeks following a baseline phase. Participants were assessed during the baseline, therapy, and follow-up phases using the Child Behavior Checklist and the Family Assessment Device. The data were analyzed visually and quantitatively. Results indicated that the treatment was effective in decreasing behavior problems and improving family functioning and that treatment effects were statistically significant and stable through the follow-up period. Research and clinical implications and limitations are discussed.

Whole-Exome Sequencing Revealed a Pathogenic Nonsense Variant in the SLC19A2 Gene in an Iranian Family with Thiamine-Responsive Megaloblastic Anemia.

Solute carrier family 19 member 2 (SLC19A2, OMIM *603941) encodes thiamine human transporter 1 (THTR-1), which contributes to bringing thiamine (vitamin B1) into cells. Mutations in SLC19A2 lead to a rare recessive genetic disorder termed thiamine-responsive megaloblastic anemia (TRMA) syndrome. An Iranian family with TRMA was investigated by whole-exome sequencing (WES) to determine the genetic cause(s) of the disease. Accordingly, SLC19A2 genetic variants were gathered through literature analysis. WES recognized a known pathogenic variant, c.697C > T (p. Q233X), within exon 2 of SLC19A2 (NM_006996). Subsequently, the proband's parents and sister were confirmed as heterozygous carriers of the identified variant. The diagnostic utility and affordability of WES were confirmed as the first approach for the genetic testing of TRMA to verify the diagnosis. This analysis can be used to guide future prenatal diagnoses and determine the consequences in the other family members.

‘Our story with the state’: Birth certificates, data structures and gay and lesbian families

Birth certificate data has been identified for its centrality in providing complete and accurate information on demographics, particularly as it relates to families. Often, however, these forms of data collection, are very much hetero-centric, re-embedding normative conceptualizations of identity, particularly as it relates to sex, gender and sexuality. Modes of demographic data collection, such as that of the birth certificate, do not allow for the fluidity and multiplicity of gender and sexual identities that characterize the lived experience of many LGBTQ families. This article will explore the significance of the birth certificate for LGBTQ Irish families, particularly in light of the varying inequalities that emerge from the data gaps they create for both parent and child. In exploring these facets, this article draws upon qualitative semi-structured interviews with LGBTQ parents, exploring how they see the data gaps that emerge on birth certificates and the effects these gaps have on them as an LGBTQ family. Through exploring the ways in which the data gaps and omissions on the Irish birth certificate creates inequalities, this article uses the findings to build on the work of Ruberg and Ruellos (2020) who call for shifting how we see and understand queer identity through data. Through these findings, we argue that systems of data collection, data structures and certification must be changed to build data for queer parenthood and that it is necessary to recalibrate how we design birth certificates to more accurately represent LGBTQ-parent families.

Homozygous AHI1 gene mutation (c.1213A>C; Thr405Pro) leads to Joubert syndrome in a consanguineous Iranian family: A case report

Joubert syndrome (JS) is an autosomal recessive (AR) neurological disorder primarily characterized by aplasia/hypoplasia of the cerebellar vermis, retinal degeneration, and a molar tooth sign (MTS) can be seen on brain imaging. This study aimed to identify JS pathogenic variant in an Iranian consanguineous pedigree. We carried out whole-exome sequencing (WES) to identify likely causal pathogenic variant in the patient. The WES analysis identified a novel homozygous missense mutation (c.1213A>C; p.T405P) in the AHI1 gene (in exon 10). The Sanger sequencing data has validated the c.1213A>C mutation. We postulated that the disease in our patient was caused by a novel homozygous missense mutation in the AHI1 gene. To the best of our knowledge, this is the first report of the AHI1 pathogenic variant causing JS phenotype in an Iranian family. Our data expand the spectrum of mutations in the AHI1 gene in JS.

ZNF142 mutation causes neurodevelopmental disorder with speech impairment and seizures: Novel variants and literature review

The ZNF142 gene on chromosome 2q35 contains ten exons and encodes a zinc finger protein 142 with 31 C2H2-type zinc fingers domain. Pathogenic variants in ZNF142 result in an autosomal recessive neurodevelopmental disorder with impaired speech and developmental delay. Here, we report two novel variants (NM_001105537: c.25C > T/c.1741C > T, p.Gln9*/p.Arg581Cys) in ZNF142 in an Iranian family identified by Whole-Exome sequencing and confirmed by Sanger sequencing. These variants are categorized as “pathogenic” and “variant of unknown significance” based on the standards for the interpretation of sequence variations recommended by ACMG, respectively. The proband is a five-year-old male born to consanguineous parents. The compound heterozygous variant (NM_001105537: c.25C > T/c.1741C > T, p.Gln9*/p.Arg581Cys) in ZNF142 was identified in the proband with moderate intellectual disability, global developmental delay, speech impairment, and seizures. This paper reported the sixth family in the world with novel pathogenic variants in the ZNF142 gene as the reason for neurodevelopmental Disorder with Impaired Speech and Hyperkinetic Movements (NEDISHM) and determining the phenotype spectrum of this disease. In this study, we also reviewed the phenotype of the former cases. In contrast to the Malaysian cases, proband in the present paper does not manifest any facial features similar to the patients in the initial study. Further studies on the NEDISHM patients could be valuable to determine the phenotype precisely.

Dilated cardiomyopathy caused by a pathogenic nucleotide variant in RBM20 in an Iranian family

IntroductionDilated cardiomyopathy (DCM) is characterized by the dilation and impaired contraction of 1 or both ventricles and can be caused by a variety of disorders. Up to 50% of idiopathic DCM cases have heritable familial diseases, and the clinical screening of family members is recommended. Identifying a genetic cause that can explain the DCM risk in the family can help with better screening planning and clinical decision-making. Whole-exome sequencing (WES) has aided significantly in the detection of causative genes in many genetically heterogeneous diseases. In the present study, we applied WES to identify the causative genetic variant in a family with heritable DCM.MethodsWES was applied to identify genetic variants on a 26-year-old man as the proband of a family with DCM. Subsequently, Sanger sequencing was performed to confirm the variant in the patient and all the available affected and unaffected family members. The pathogenicity of the variant was evaluated through co-segregation analysis in the family and employment of in silico predictive software.ResultsWES demonstrated the missense pathogenic heterozygous nucleotide variant, c.1907G > A, (p.Arg636His, rs267607004, NM_0011343), in exon 9 of the RBM20 gene in the proband. The variant was co-segregated in all the affected family members in a heterozygous form and the unaffected family members. The in silico analysis confirmed the variant as pathogenic.ConclusionPathogenic RBM20 nucleotide variants are associated with arrhythmogenic DCM. We believe that our report is the first to show an RBM20 variant in Iranian descent associated with DCM.

The lived experience of bereaved Iranian families with COVID-19 grief

The present study investigated the lived experience of bereaved family members from grief due to COVID-19 using descriptive phenomenological method via in-depth interviews. The participants (N = 30) were spouses, children, parents, and siblings of the deceased. The obtained data from interviewing were analyzed using Colaizzi’s method. Eight main themes were obtained. Findings suggest that society is confronted with the prolonged grief on a large scale and has put people in an existential experience situation. Different experiences, which have led to creation of new meaning in loss and life, has been able to help some post-traumatic growth in the bereaved.

Wde, calpA, if, dap160, and poe genes knock down Drosophila models exhibit neurofunctional deficit

Intellectual disability (ID) is a heterogeneous disorder with high prevalence and remarkable social and cost burdens. Novel genetic variants of ATF7IP, CAPN9, ITGAV, ITSN1, and UBR4 genes are reported to be associated with the ID among Iranian families. However, in vivo validation is required to confirm the functional role of these variants in ID development. Drosophila melanogaster is a convenient model for such functional investigations as its genome bears ortholog of more than 75% of the disease-causing genes in human and represents numerous approaches to study defects in neuronal function. In this connection, RNAi gene silencing was applied to wde, calpA, if, dap160, and poe genes, the Drosophila ortholog of the selected human genes, and then consequent structural and functional changes in neurons were studied by means of immunohistochemistry and confocal microscopy of mushroom bodies (MBs) and validated behavioural assays including larvae and adult conditioning learning and memories, and ethanol sensitivity. Down-regulation of these genes led to neuronal loss which was evident by decline in total fluorescent signal intensity in micrographs of MBs structure. The gene silencing caused neuronal dysfunction and induction of ID-like symptoms manifested by deficits in larval preference learning, and short-term olfactory memory and courtship suppression learning in adults. Moreover, the RNAi flies showed higher sensitivity to ethanol vapour. Interestingly, the poe knock-down flies exhibited the most severe phenotypes among other genes. Altogether, we believe this study is first-of-its-kind and findings are highly applicable to confirm pathogenecity of the selected ID gene variants in Iranian population.

Co-segregation of variant NSUN2 Lue198Arg among Iranian family with intellectual disability: a case report

BackgroundIntellectual disability is characterized by impairments in adaptive behavior and cognitive functioning manifested during the developmental period. Since disabilities are heterogeneous, variant analysis can help us confirm and accurately diagnose children with intellectual disabilities. Some papers reported that bi-allelic variants of the NSUN2 gene caused a group of neurological disorders, including non-syndromic autosomal recessive intellectual disability (NS-ARID), Dubowitz syndrome, and familial restrictive cardiomyopathy 1 (RCM1). We report on a consanguineous family with three siblings diagnosed with intellectual disability.Case presentationThe 7-year-old female was referred to Ali-Asghar hospital, Zahedan, Iran, with clinical manifestations comprising moderate intellectual disability, ptosis, long face, and short stature. Chromosome banding, metabolic testing, and magnetic resonance imaging examinations revealed no abnormalities. Accordingly, other affected siblings born of the same parents were considered. Whole-exome sequencing (WES) was conducted on the sufferer to consider NS-ARID variants. Findings identified a variant with uncertain significance (NM_017755.6: c.593 T > G) in the NSUN2 gene in the proband. This variant was confirmed through Sanger sequencing of the affected and unaffected family members. Besides, the computational results showed that the L198R exchange could change the interaction between wild-type and other residues in the protein. The affected patients with NS-ARID had similar clinical characteristics and genetic abnormalities.ConclusionTaken together, we described the variant in three Iranian siblings; further expanding of the other variants involved in the disease will be evident by using high-throughput sequencing technologies.

Phenotype of a second Irish variant causing hereditary amyloidogenic transthyretin amyloidosis

Hereditary amyloidogenic transthyretin (ATTR) amyloidosis is an autosomal dominant, multi-systemic and progressive disorder characterised by polyneuropathy, cardiomyopathy and dysautonomia to varying degrees. In Ireland, the p.Thr80Ala mutation has been well documented, but little has been reported about a second variant, the p.His110Asp mutation first discovered in a family native to county Cork. Here we elaborate on the phenotype of this recently identified mutation using an extended pedigree of the original kindred and include for the first time a second affected family. Patients attending our centre with confirmed or suspected ATTR amyloidosis as a result of a p.His110Asp mutation were identified. Detailed chart reviews and patient interviews were completed. Data on symptoms, examination findings, neurophysiology, histology, biochemistry, and cardiac investigations were gathered. A large extended pedigree was plotted. A total of 17 members across four generations of one kindred, and 2 members of a previously unreported family were identified. A phenotype of progressive late-onset polyneuropathy with cardiac involvement was common to both families. An early manifestation was carpal tunnel syndrome, preceededing neuropathy by many years. Gastrointestinal and urinary symptoms were common. We describe a wider phenotype of the p.His110Asp mutation of transthyretin in two Irish families. Importantly, we describe cardiac involvement which was not previously emphasised. The discovery of a new unrelated family highlights the importance of clinical suspicion even in those without known family history. We suggest that this second important transthyretin mutation should be considered in patients of Irish origin.

Investigating the Preparedness of Iranian Families in the Face of Disasters.

Preparedness in different sections of a society can improve the reactions of individuals at the time of disasters and strengthen the cooperation and coordination between people and organizations. The present study aimed to investigate the preparedness of households in Ardabil Province of Iran in the face of disasters in 2020. This descriptive, cross-sectional study was conducted in Ardabil Province in Iran in 2020. The target population included the households living in Ardabil Province. The study was conducted on 10 502 participants. The data were collected using a questionnaire completed by trained questioners by referring to the participants' houses. It should be noted that the questionnaires were completed by one of the household parents. The questionnaire contained 15 questions related to taking and not taking disaster preparedness measures at specific times. EXCEL 2016 (Microsoft, Redmond, WA) and SPSS 23 software (IBM Corp, Armonk, NY) were used for data analysis. Considering the score of 1 for each action, the mean score of households' disaster preparedness in Ardabil Province was 31.09%. The preparedness level of 51.4%, 42.31%, and 6.29% of the households in the province against disasters was at low, moderate, and good levels, respectively. Among the items of preparedness in the face of disasters, the highest value was related to the familiarity of family members with the initial warnings of significant hazards (5162 households, 49.15%) followed by planning for coping with disasters (43.12%) and assessing the non-structural vulnerability (38.93%). Furthermore, the results showed that the level of household preparedness was higher in the center of the province compared to other cities. Evaluating the level of preparedness of different societies in the face of disasters can be very useful in identifying the challenges to improve preparedness and, consequently, achieving sustainable development. This assessment can be considered a resource for provincial policy-making and planning to achieve the priorities set out in the Sendai framework. However, such assessments should be performed periodically, for example, annually, to reflect the effectiveness of the interventional measures in improving preparedness. Considering the low level of households' preparedness in the present study, there is a gap between what people know and what they do, and comprehensive studies are needed on various factors that encourage people to take preparedness measures.

MCM2 mutation causes autosomal dominant nonsyndromic hearing loss (DFNA70): novel variant in the second family

Pathogenic variants in MCM2 could result in mild to severe sensorineural hearing loss in the affected individuals (deafness, autosomal dominant 70; DFNA70; OMIM: 616968), an extremely rare autosomal dominant progressive disorder. Here, we report a novel missense variant (NM_004526:c.388C>T, p.R130C; Clinvar: SCV002072508) in MCM2 in an Iranian family identified by whole-exome sequencing and confirmed by Sanger sequencing. The heterozygous variant (NM_004526:c.388C>T, p.R130C) in MCM2 was identified in the proband and his mother. The proband is a nine-year-old male born to nonconsanguineous parents. The proband was characterized by nonsyndromic hearing loss, while his mother showed a mild form of the disorder. This study reports the second disease-causing variant in MCM2 in the world and confirms that hearing loss arising from variants in MCM2 is nonsyndromic. Nevertheless, as was reported in the previous family, phenotype could vary among the patients with the same variant.

Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies in a consanguineous Iranian family is associated with a homozygous start loss variant in the PRUNE1 gene

BackgroundHomozygous or compound heterozygous PRUNE1 mutations cause a neurodevelopmental disorder with microcephaly, hypotonia, and variable brain malformations (NMIHBA) (OMIM #617481). The PRUNE1 gene encodes a member of the phosphoesterase (DHH) protein superfamily that is involved in the regulation of cell migration. To date, most of the described mutations in the PRUNE1 gene are clustered in DHH domain.MethodsWe subjected 4 members (two affected and two healthy) of a consanguineous Iranian family in the study. The proband underwent whole-exome sequencing and a start loss identified variant was confirmed by Sanger sequencing. Co-segregation of the detected variant with the disease in family was confirmed.ResultsBy whole-exome sequencing, we identified the a start loss variant, NM_021222.3:c.3G>A; p.(Met1?), in the PRUNE1 in two patients of a consanguineous Iranian family with spastic quadriplegic cerebral palsy (CP), hypotonia, developmental regression, and cerebellar atrophy. Sanger sequencing confirmed the segregation of the variant with the disease in the family. Protein structure analysis also revealed that the variant probably leads to the deletion of DHH (Asp-His-His) domain, the active site of the protein, and loss of PRUNE1 function.ConclusionWe identified a start loss variant, NM_021222.3:c.3G>A; p.(Met1?) in the PRUNE1 gene in two affected members as a possible cause of NMIHBA in an Iranian family. We believe that the study adds a new pathogenic variant in spectrum of mutations in the PRUNE1 gene as a cause of PRUNE1-related syndrome.

An Interethnic Paradox: Chicago's Irish and Everyone Else

An Interethnic Paradox: Chicago's Irish and Everyone Else

Development and Psychometric Evaluation of Family Caregivers' Hardiness Scale: A Sequential-Exploratory Mixed-Method Study.

ObjectiveCaring for patients with Alzheimer’s disease (AD) is a stressful situation and an overwhelming task for family caregivers. Therefore, these caregivers need to have their hardiness empowered to provide proper and appropriate care to these older adults. From the introduction of the concept of hardiness, few studies have been conducted to assess the hardiness of caregivers of patients with AD. Presumably, one reason for this knowledge gap is the lack of a proper scale to evaluate hardiness in this group. This study was conducted to develop a reliable and valid Family Caregivers’ Hardiness Scale (FCHS) to measure this concept accurately among Iranian family caregivers sample.MethodsThis study is a cross-sectional study with a sequential-exploratory mixed-method approach. The concept of family caregivers’ hardiness was clarified using deductive content analysis, and item pools were generated. In the psychometric step, the samples were 435 family caregivers with a mean age of 50.26 (SD ± 13.24), and the data were gathered via an online form questionnaire. In this step, the items of the FCHS were evaluated using face and content validity. Then, the factor structure was determined and confirmed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) followed by convergent and divergent validity, respectively. Finally, scale reliability, including stability, and internal consistency were evaluated.ResultsThe finding revealed that FCHS consists of five factors, namely, “Religious Coping” (5 items), “Self-Management” (6 items), “Empathic Communication” (3 items), “Family Affective Commitment” (3 items), and “Purposeful Interaction” (4 items) that explained 58.72% of the total variance. The results of CFA showed a good model fit. Reliability showed acceptable internal consistency and stability.ConclusionBased on the results of the psychometric evaluation of the FCHS, turned out that the concept of hardiness in Iranian family caregivers is a multidimensional concept that is most focused on individual-cultural values, emotional family relationships, and social relationships. The designed scale also has acceptable validity and reliability features that can be used in future studies to measure this concept in family caregivers.