Erratum: The genomic architecture of NLRP7 is Alu rich and predisposes to disease-associated large deletions

NLRP7 is a major gene responsible for recurrent hydatidiform moles. Here, we report 11 novel NLRP7 protein truncating variants, of which five deletions of more than 1-kb. We analyzed the transcriptional consequences of four variants. We demonstrate that one large homozygous deletion removes NLRP7 transcription start site and results in the complete absence of its transcripts in a patient in good health besides her reproductive problem. This observation strengthens existing data on the requirement of NLRP7 only for female reproduction. We show that two other variants affecting the splice acceptor of exon 6 lead to its in-frame skipping while another variant affecting the splice donor site of exon 9 leads to an in-frame insertion of 54 amino acids. Our characterization of the deletion breakpoints demonstrated that most of the breakpoints occurred within Alu repeats and the deletions were most likely mediated by microhomology events. Our data define a hotspot of Alu instability and deletions in intron 5 with six different breakpoints and rearrangements. Analysis of NLRP7 genomic sequences for repetitive elements demonstrated that Alu repeats represent 48% of its intronic sequences and these repeats seem to have been inserted into the common NLRP2/7 primate ancestor before its duplication into two genes

Yunis-Varón Syndrome: The First Report of Two Iranian Cases

The Yunis-Varón syndrome represents a rare autosomal recessive syndrome of easy recognition characterized by defective growth of the cranial bone along with complete or partial absence of the clavicles (cleidocranial dysplasia), absence of thumbs and halluces, distal aphalangia, ectodermal anomalies, growth retardation and poor outcome. The molecular genetic basis is unknown. Here, we report an 8 months old girl with Yunis-Varón syndrome, born to a consanguineously married, with normal parents. She had micrognathia, wide fontanels, prominent eyes, poor sucking, congenital heart diseases, asymmetric face, ambiguous genitalia, reduction anomaly in right hand including thumb, and hypoplastic distal phalanges of 3th fingers, and hypo plastic clavicles. She has glaucoma and lenses opacity. There is another similar case in her family. Karyotype is normal. She is the first Iranian known case of Yunis-Varón syndrome

Fraccaro Syndrome: Report of Two Iranian Cases: An Infant and an Adult in A Family

49,XXXXY is rare chromosomal pattern and these patients have mental retardation, small penis, cryptorchidism and skeletal anomalies. We reported a 10 month-old boy who has hypotonia, microcephaly, hypertelorism, depressed nasal bridge, epicanthic folds and bilateral multiple ear tags, high arched palate, down set ears, micrognathia and congenital heart disease such as patent ductus arteriosus (PDA), Atrial septal defect (ASD), mild pulmonary stenosis. Among the skeletal anomalies, he has kyphoscoliosis, clinodactyly of the fourth and fifth fingers of both hands, and bilateral club foot and unilateral dysplasia of the hip. Karyotype was found as 49,XXXXY[44]/48,XXXY[6] and this cytogenetic analysis was help to establish clinical diagnosis Fraccaro syndrome

The Prevalence of Children’s Postural Abnormalities and Its Association with Sport Activity

Background & Objective: The future of each society is based on its youth. In addition, the physical-mental health as well as the presence of healthy and capable people is a considerable requirement for all the societies. Thus, the aim of this research was to study the prevalence rate of children’s postural abnormalities and its relationship with sport activity. Materials & Method: 148 children (74 boys and 74 girls) were randomly selected. The research tools were plummet (guideline), matrix sheet, mirror box and the personal characteristics questionnaire. All the results were analyzed by using chi-square, freedman statistical method and the spearman correlation coefficient. Result: The results indicated that there is a significant difference between the two normal and abnormal height structure states (p≤0.01). Similarly, there was a significant negative difference between the number of skeletal abnormalities and the exercise activities in girls (r= 0.355) and boys (r= 0.369). In the case of abnormalities comparison between the sexes, the freedman test results indicated that there is a significant difference between the ranking of the boys’ skeletal abnormalities as compared to the girls, in a way that the dorsal lord sis and flat back were the highest and the lowest in the girls, respectively. Moreover, the results of the person correlation coefficient test indicated that there is only a positive significant relationship between the age of the girls and the number of skeletal abnormalities (p≤0.01, r=0.586). Conclusions: According to the results of this research, it can be stated that majority of the children at least have single skeletal abnormality, resulted from some factors such as heredity, daily wrong habits, and non standard equipments and facilities. In addition, not attending the related sports activities may increase the chance of these skeletal abnormalities

Fanconi-Bickel syndrome versus osteogenesis imperfeeta: An Iranian case with a novel mutation in glucose transporter 2 gene, and review of literature

Fanconi-Bickel syndrome is an extremely rare hereditary metabolic disease, characterized by hepatomegaly due to glycogen storage, refractory hypophosphatemic rickets, marked growth retardation and proximal renal tubular acidosis. Recurrent bone fractures are one of the hallmark findings. It is a single gene disorder; the responsible gene belongs to the facilitative glucose transporters 2 (GLUT2) family gene or (SLC2A2) mapped to the q26.1-26.3 locus on chromosome 3, and encodes the GLUT protein 2. This protein is expressed in pancreatic ί-cells, hepatocytes, renal tubules, and intestinal mucosa. Several mutations in the GLUT2 gene have been reported in different ethnicities. Herein we report an Iranian girl with a missed diagnosis of osteogenesis imperfecta. She was referred with the history of frequent fractures, and severe motor delay and was suspected to osteogenesis imperfecta. Following the case we detected refractory rickets instead of OI, sever growth failure, proximal renal tubulopathy and RTA, and enlarged kidneys, progressive hepatomegaly, and GSD on liver biopsy. Glucose and galactose tolerance tests confirmed abnormal carbohydrate metabolism. Molecular analysis on GLUT2 gene revealed a homozygous novel mutation in exon 5; it was 15 nucleotide deletion and 7 nucleotide insertion and caused a frame shift mutation, produced a premature truncated protein (P.A229QFsX19). This mutation has not been reported before in the relevant literature

Phenotypical characterization of 13q deletion syndrome: Report of two cases

Patients with 13q deletion syndrome are characterized with different phenotypical features depending on the size and location of the deleted region on chromosome 13. These patients fall into three groups: In Group 1, deleted region is in the proximal and does not extend into q32; in Group 2, deleted region involves proximal to the q32 and in Group 3 q33-q34 is deleted. We present two cases with 13q syndrome with two different deleted region and different severity on clinical features: One case with interstitial deletion belongs to the Group 1 with mild mental retardation and minor malformations and the other case with terminal deletion belongs to Group 3 with moderate to severe mental retardation and major malformations

COVID-19 and Thalassaemia in Iran

Coronavirus disease 2019 (COVID-19) has had and continues to have a significant medical, public health, social and economic impact on every society around the world. Some groups of chronic patients including thalassaemia and other haemoglobin disorders were considered from the beginning of the pandemic, as vulnerable and high risk ones with regards to a more severe clinical outcome of the infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). This is because patients with thalassaemia can present with many and multiple co-morbidities including diabetes, heart, liver, endocrine and other conditions mainly secondary to iron overload and consequent to ineffective or suboptimal medical care and/or adherence to chelation treatment in particular. Transfusion dependent patients with β-thalassaemia have been greatly affected across the world, including in Iran, a country geographically situated in the so called thalassaemia belt. Iran with about 20,000 patients with β-thalassaemia and quite successful disease specific prevention and management national programmes faced challenges similar to others. Blood shortages for example consequent to COVID-19 precaution measures taken in every country to contain the virus and the difficulties in accessing drugs including lifesaving ones (iron chelation medication) constitute major challenges. In Iran however, and despite the multiple difficulties as described above, SARS-CoV-2 had a rather small impact regarding infection rates as compared to the rest of the countries, albeit a higher mortality rate reaching 26.5% amongst COVID-19 diagnosed patients. More comprehensive data however from a bigger number of patients with thalassaemia across the world infected with SARS-CoV- 2 is necessary to draw any reliable conclusions as to the level of vulnerability to SARS-CoV-2 and importantly the clinical impact of this virus in these patients

Iranian Patients’ Attitudes to Current and Novel Therapies: A Patient Directed Survey

Thalassemia is one of the important challenges of the health system in Iran. Recently the medicinal drug of luspatercept and gene therapy have opened new horizons for thalassemia treatment. The present article aims to evaluate the attitude of thalassemics in Iran about the new treatments. In this research, data collection through the virtual space has been practiced. The patients were required to declare their opinion on the aforementioned treatments. Finally, 128 male and 204 female plus 1 who did not specify their gender answered the questions. The results showed that despite patients’ positive attitude towards new treatments, their treatment experiences as well as the expenses of the new treatment practices are cause of concern. Moreover, the social problems like unemployment among thalassemics place impact on their perspective about treatment changes. Based on the findings of the present research, providing patients with more information about new treatment regimen and making the their expenses compatible with the economic status of the developing countries would be effective in making the new treatments accessible to all eligible patients

The point mutations of m itochondrial tRNA threonine and proline in idiopathic repeated pregnancy loss

Background: Mitochondrial transfer RNAs (tRNA) genes are essential components of protein biosynthesis. These genes are hotspots for mutations. These mutations are associated with a wide spectrum of human disease. Many genetic factors are known in assessment of repeated pregnancy loss (RPL). Objective: The aim of this study was analysis of tRNA Thr and tRNA Pro in women with RPL. Materials and Methods: The nucleotide variations of threonine and proline were investigated in 96 women with idiopathic repeated pregnancy loss. The related mitochondrial area was amplified using a polymerase chain reaction (PCR). The PCR products were demonstrated by 2% agarose gel electrophoresis, and all the positive samples were purified and verified by an automated DNA sequencing method. Results: The sequence analysis revealed 4 mutations in tRNA Thr. These mutations were A15907G in 2 cases (2.08%), A15924G in 3 cases (3.12%), G15928A in 10 cases (10.42%) as the most common mutations and G15930A in 3 cases (3.12%) as a novel mutation. Also, the result of tRNApro sequencing showed the T15972C mutation in 1 woman (1.04%) as a novel mutation. Conclusion: These tRNAs mutations can alter their steady state level and affect the structure of tRNAs. It results in protein synthesis defects and, in turn, mitochondrial dysfunction. The mutations of these genes may help in the assessment of RPL. Further study of an expanded series of these tRNA mutants is recommended to describe their etiologic role in idiopathic RPL