Familial Undercurrents

Not long after her father died, Afsaneh Najmabadi discovered that her father had a secret second family and that she had a sister she never knew about. In Familial Undercurrents, Najmabadi uncovers her family’s complex experiences of polygamous marriage to tell a larger story of the transformations of notions of love, marriage, and family life in mid-twentieth-century Iran. She traces how the idea of “marrying for love” and the desire for companionate, monogamous marriage acquired dominance in Tehran’s emerging urban middle class. Considering the role played in that process by late nineteenth- and early twentieth-century romance novels, reformist newspapers, plays, and other literature, Najmabadi outlines the rituals and objects---such as wedding outfits, letter writing, and family portraits---that came to characterize the ideal companionate marriage. She reveals how in the course of one generation men’s polygamy had evolved from an acceptable open practice to a taboo best kept secret. At the same time, she chronicles the urban transformations of Tehran and how its architecture and neighborhood social networks both influenced and became emblematic of the myriad forms of modern Iranian family life.

Homozygous SOD1 Variation L144S Produces a Severe Form of Amyotrophic Lateral Sclerosis in an Iranian Family

ObjectivesAmyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by degeneration of motor neurons determining progressive muscular atrophy, weakness, and death from respiratory failure.MethodsHere, we report clinical and molecular findings of a novel Iranian family affected with a severe form of early-onset familial ALS.ResultsThree siblings born to consanguineous parents developed a form of ALS characterized by early-onset lower limb involvement and a fast progression, proving fatal at age 16 years for 1 of them. Molecular analysis of the SOD1 gene revealed the homozygous substitution c.434T>C in exon 5 resulting in the amino acid change p.Leu144Ser (L144S), previously reported as a dominant variant. Both parents were heterozygous carriers. The probands' mother recently developed a late-onset ALS with predominant upper motor neuron involvement.DiscussionThis report adds p.L144S to the short list of homozygous SOD1 variants and suggests that the development of an earlier-onset and/or faster disease progression can occur when 2 mutated alleles are present.

Dinamika Hukum Keluarga Islam dan Isu Gender di Iran: Antara Pemikiran Elit Sekuler dan Ulama Islam

This article examines the dynamics of family law in the Islamic Republic of Iran where there are upheavals and struggles between the secular elites and ulama from 1927 to the present day. This study applied a library research by digging up information related to the theme of the study. The results of this study indicate that the Islamic Republic of Iran is dominantly Shia Imamiyyah (Jafari) but it also accommodates the Hanafi (Sunni) School in the field of marriage law. Iranian family law has gone through many changes. Since 1928 the issue of divorce and marriage which was originally regulated in Irans Qanun Madani came into force in 1930, the Marriage Law was then enacted in 1931. After three decades, in 1967 there was a reformation, the Marriage Law was replaced by the Family Protection act, then it was replaced with the Protection of Family in 1975. These laws are a combination of Islamic Law and French civil Jurisprudence, though they seem more secular. However, since the Iranian Revolution in 1979, these laws have been abolished and all laws in Iran have been returned to sharia law. As a result, the laws become repressive against women, except in the field of inheritance which provides gender equality. While there have been many highly educated women in Iran, since 2006 many women have filed for divorce. On the other hand, the practice of mutah marriage has begun to be abandoned and polygamy is opposed by the community.

Whole-exome sequencing identified compound heterozygous variants in the TTN gene causing Salih myopathy with dilated cardiomyopathy in an Iranian family

Background: Salih myopathy, characterised by both congenital myopathy and fatal dilated cardiomyopathy, is an inherited muscle disorder that affects skeletal and cardiac muscles. TTN has been identified as the main cause of this myopathy, the enormous size of this gene poses a formidable challenge to molecular genetic diagnostics. Method: In the present study, whole-exome sequencing, cardiac MRI, and metabolic parameter assessment were performed to investigate the genetic causes of Salih myopathy in a consanguineous Iranian family who presented with titinopathy involving both skeletal and heart muscles in an autosomal recessive inheritance pattern. Results: Two missense variants of TTN gene (NM_001267550.2), namely c.61280A>C (p. Gln20427Pro) and c.54970G>A (p. Gly18324Ser), were detected and segregations were confirmed by polymerase chain reaction-based Sanger sequencing. Conclusions: The compound heterozygous variants, c.61280A>C, (p. Gln20427Pro) and c.54970G>A, (p. Gly18324Ser) in the TTN gene appear to be the cause of Salih myopathy and dilated cardiomyopathy in the family presented. Whole-exome sequencing is an effective molecular diagnostic tool to identify the causative genetic variants of large genes such as TTN.

Identification of a Novel Homozygous Mutation in BBS10 Gene in an Iranian Family with Bardet-Biedl Syndrome

Background: Bardet–Biedl Syndrome (BBS) is a rare pleiotropic autosomal recessive disease related to ciliopathies with approximately 25 causative genes. BBS is a multisystemic disorder with wide spectrum of manifestations including truncal obesity, retinal dystrophy, male hypogenitalism, postaxial polydactyly, learning difficulties, and renal abnormalities. Methods: A consanguineous Iranian family with a 28-year-old daughter affected with BBS, resulting from a first cousin marriage, was examined. After clinical examination, Whole Exome Sequencing (WES) was applied. Following the analysis of exome data, Sanger sequencing was used to confirm as well as to co-segregate the candidate variant with the phenotype. Results: A novel homozygous variant [c. 2035G>A (p.E679K)] in exon 2 of the BBS10 gene was found which was categorized as likely pathogenic based on American College of Medical Genetics and Genomics (ACMG) guidelines and criteria. In this study, the variant was fully co-segregated with the phenotype in the family. Conclusion: Despite overlapping with other ciliopathies in terms of the phenotype, the BBS has high genetic heterogeneity and clinical variability even among affected members of a family. The symptoms observed in patients are largely related to the genes involved and the type of mutations in the BBS. In this study, in addition to phenotype description of the proband harboring a novel disease-causing variant in BBS10 gene, the spectrum of BBS symptoms was expanded. The findings of this study can be useful in genetic counseling, especially for risk estimation and prenatal diagnosis.

Waardenburg syndrome type 2A in a large Iranian family with a novel MITF gene mutation

Background The characteristics of Waardenburg syndrome (WS) as a scarce heritable disorder are sensorineural hearing loss and deficits of pigmentation in the skin, hair, and eye. Here, clinical features and detection of the mutation in the MITF gene of WS2 patients are reported in a sizable Iranian family. Methods A man aged 28-years represented with symptoms of mild unilateral hearing loss (right ear), complete heterochromia iridis, premature graying prior to 30 years of age, and synophrys. In this research, there was a sizable family in Iran comprising three generations with seven WS patients and two healthy members. Whole exome sequencing was applied for proband for the identification of the candidate genetic mutations associated with the disease. The detected mutation in proband and investigated family members was validated by PCR-Sanger sequencing. Results A novel heterozygous mutation, NM_198159.3:c.1026dup p.(Asn343Glufs*27), in exon 9 of the MITF gene co-segregated with WS2 in the affected family members. The variant was forecasted as a disease-causing variant by the Mutation Taster. According to the UniProt database, this variant has been located in basic helix-loop-helix (bHLH) domain of the protein with critical role in DNA binding. Conclusions A frameshift was caused by a nucleotide insertion, c.1026dup, in exon 9 of the MITF gene. This mutation is able to induce an early termination, resulting in forming a truncated protein capable of affecting the normal function of the MITF protein. Helpful information is provided through an exactly described mutations involved in WS to clarify the molecular cause of clinical characteristics of WS and have a contribution to better genetic counseling of WS patients.

Neurodevelopmental Disorder With Microcephaly, Hypotonia, And Variable Brain Anomalies In A Consanguineous Iranian Family Is Associated With A Novel Homozygous Start Loss Variant In The PRUNE1 Gene

Background: Homozygous 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. Methods: We subjected 4 members (two affected and two healthy) of a consanguineous Iranian family in the study. The proband underwent whole-exome sequencing and a novel identified variant was confirmed by Sanger sequencing. Co-segregation of the detected variant with the disease in family was confirmed.Results: By whole-exome sequencing, we identified the first 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. Conclusion: We identified a novel 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.