Systemic aspergillosis in a patient with interferon gamma receptor 1 deficiency; a case report.

BACKGROUND: Interferon-gamma receptor deficiency is a heterogeneous spectrum of disease which involves mutations in IFNGR1, IFNGR2 genes, and the downstream signaling proteins such as STAT1. These mutations are associated with immunodeficiency 27 A and 27B, making the patient prone to mycobacterial infections. Patients with this condition are also at increased risk for affliction with viral and bacterial infections, such as with the Herpesviridae family, Listeria, and Salmonella. Moreover, SH2B3 mutation is associated with autoimmune and lymphoproliferative conditions. CASE PRESENTATION: the patient was a 19-month-old infant girl who presented with a two-week history of fever. She had near-normal flowcytometry with high IgM and IgE. She had pneumonic infiltration in her chest and right hilar and para-aortic lymphadenopathy. PCR of whole blood for Aspergillus fumigatus came back positive. In her Whole Exome Sequencing she had IFNGR1 and SH2B3 mutations. CONCLUSION: systemic fungal infections such as Aspergillosis can occur in patients with interferon-gamma receptor one deficiency. This type of immunodeficiency should be considered in treating patients with systemic Aspergillosis.

The effect of vitamin D add-on therapy on the improvement of quality of life and clinical symptoms of patients with chronic spontaneous urticaria.

BACKGROUND: Chronic urticaria is a common distressing allergic skin disorder. Immune dysregulation, histamine release and mast cell degranulation are suggested as its underlying mechanisms. OBJECTIVE: Add-on therapy of vitamin D was evaluated in patients with chronic spontaneous urticaria to determine the quality of life and urticaria severity score. METHODS: In a prospective, double-blinded study, 80 participants with chronic spontaneous urticaria were randomized to low (4200 IU/week, group 1) and high (28,000 IU/week, group 2) vitamin D3 supplementation groups for 12 weeks. Demographic data; quality of life, urticaria severity and medication scores; 25-hydroxyvitamin D and anti-thyroid peroxidase antibody levels; and autologous serum skin test data were collected. RESULTS: Both groups showed significantly reduced total urticaria severity score; decrement in group 2 score was significant compared to group 1 at week 6 (P = 0.010). Quality of life score was also significantly reduced; decrement in group 2 score was significant compared to group 1 at both weeks 6 (P = 0.005) and 12 (P = 0.007). 25-hydroxyvitamin D levels were elevated significantly over the course of 12 weeks in both groups; however, the elevation in group 2 was significantly higher than group 1 at week 12 (P = 0.002). Medication score was significantly reduced, with no significant difference between groups. No association was observed between positive autologous serum skin test, angioedema and high level of Anti thyroperoxidase antibody with positive response to vitamin D. CONCLUSIONS: Add-on therapy with vitamin D (28,000 IU/week) can be considered as a safe and potentially beneficial treatment in patients with chronic spontaneous urticaria.

Assessing the Association of Kawasaki Disease Symptoms and Echocardiographic Findings.

Kawasaki disease is an acute systemic vasculitis which can cause cardiac involvement among other symptoms. In this study we aimed to assess the relationship between the echocardiographic findings of Kawasaki disease with the clinical and paraclinical findings of the patients. In this cross-sectional study, the symptoms of 307 Kawasaki patients were registered and the association of the symptoms with paraclinical findings and echocardiographic studies was assessed. 190 (61.9%) of the patients were male and 117 (38.1%) were female. 193 patients (62.9%) did not have any abnormalities in their echocardiography, while others showed coronary artery aneurysms, perivascular brightness, coronary artery dilatation, and trivial Mitral Regurgitation in their echocardiography. A significant inverse relationship was seen with echocardiographic findings and age. Thrombocytosis, conjunctivitis, and oral and/or pharyngeal erythema and/or strawberry tongue were associated with higher rates of echocardiographic abnormalities. Echocardiographic abnormalities are associated with younger age, higher platelets, and the existence of conjunctivitis and oral and/or pharyngeal erythema and/or strawberry tongue.

Investigating the association of atopy and aeroallergen sensitization and chronic spontaneous urticaria.

Introduction: Chronic spontaneous urticaria (CSU) is a common skin allergic reaction with an unknown mechanism. There is inadequate evidence to support the role of aeroallergen sensitization in CSU. Aim: The present study was conducted to investigate the association between the aeroallergen sensitivity and CSU. Material and methods: In this cross-sectional study, 91 patients with CSU were recruited. Information on demographic characteristics was collected. The skin prick test (SPT) for most prevalent aeroallergens and pulmonary function test (PFT) were performed and the results were clinically matched to investigate the allergic rhinitis (AR) and asthma. Total serum immunoglobulin E (IgE) concentration was analysed in the subjects for the presence of atopy. Results: Ninety one patients (75 of them were females) were enrolled in the study (with a mean age of 36.90 ±12.93 years). SPT result was positive in 75 (82.4%) subjects. Weeds (67 cases, 73.6%), trees (61 cases, 67%), and dust mites (55 cases, 60.4%) were the most common pollens in the positive SPT samples. Thirty-seven (40.7%) of the patients had allergic rhinitis. There was a statistically significant association between the presence of AR and positive SPT result (p = 0.002). Eight patients had allergic asthma and 45 (49.4%) of the patients had a total serum IgE level of more than 100 IU/ml. Conclusions: Our results indicated a clear association between the presence of aeroallergen sensitivity and development of CSU. AR exists as a co-morbidity of CSU.

Epidemiology, Sociodemographic Factors and Comorbidity for Allergic Rhinitis, Asthma, and Rhinosinusitis Among 15 to 65-year-Old Iranian Patients.

Background: It is well established that upper and lower airways are often clumped together when diagnosing and treating a disease. This study was designed to determine the prevalence of upper and lower airway diseases and to assess the effect of sociodemographic factors on the prevalence and the comorbidity of these disorders. Methods: This cross-sectional population-based study included patients with ages ranging between 15 to 65 years, who were referred to allergy outpatient clinics in various provinces of Iran from April to September 2020. A modified global Allergy and Asthma European Network (GA2LEN) screening questionnaire was filled out by local allergists of the 12 selected provinces in Iran. Information about the patients and sociodemographic factors was also recorded. Statistical analysis was done by univariate statistical analyses and multiple logistic regressions in SPSS software Version 26. Results: Out of 4988 recruited patients, 1078 (21.6%) had the symptoms of allergic rhinitis (AR) and 285 (5.7%) met the criteria of asthma. The prevalence of acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) was 21.6 % and 22%, respectively. The highest prevalence of AR and ARS was in Tehran with the arateof of 33.9% each. Asthma was more prevalent in Khuzestan (14.2%) and CRS in Baluchestan (57.5%). Our analysis showed that the patients with asthma were most likely to have other allergic diseases as well-CRS (OR = 4.8; 95% CI, 2.02- 5.82), AR (OR= 2.5, 95% CI, 2.10-3), ARS (OR = 1.8; 95% CI, 2.10-3), followed by eczema (OR = 1.4; 95% CI, 1.13-1.67).We found that those individuals with CRS were most likely to have painkiller hypersensitivity (OR= 2.1; 95% CI, 1.21-3.83). Furthermore, smoking has been found more than 1.5 folds in patients with ARS. After adjusting variables, there was no correlation between education, occupation, and ethnicity with the studied diseases. Conclusion: Rhinosinusitis is a common condition among Iranian patients. This study confirmed that inflammation of the upper and lower airways can occur simultaneously. Gender, education, occupation, and ethnicity were found to be irrelevant in the development of either AR, asthma, ARS, or CRS.

Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity.

BACKGROUND: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations. METHODS: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data. RESULTS: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5%) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4%). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0%), ATM (in 13 patients, 14.0%), and BTK (in 9 patients, 10.0%) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100%), 3 of 3 AIRE (100%), and 21 of 30 LRBA (70.0%) mutated genes had the highest prevalence of autoimmunity. CONCLUSIONS: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease.

Efficacy of the colchicine add-on therapy in patients with autoimmune chronic urticaria.

Chronic urticaria is in some cases very difficult to treat, we aimed to evaluate the effect of colchicine on chronic urticaria management. Fifty-five euthyroid patients with chronic urticaria were examined based on UQL and UAS7 questionnaires. The overall UQL-Q score after 3 months has not any statistical difference between groups. The overall UQL-Q score changes between groups was not statistically different. However, the UQL-Q score significantly reduces during study period in each group. In conclusion, colchicine can manage the sign and symptoms of chronic urticaria, which improve the patients' quality of life.

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity.

BACKGROUND: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. METHODS: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. RESULTS: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. CONCLUSION: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.

Efficacy of oral supplementation of whey protein in patients with contact dermatitis: A pilot randomized double-blind placebo-controlled clinical trial.

Whey protein is a popular dietary product that has numerous health benefits such as immune modulation. In this study, we assessed efficacy of whey protein in management of patients with contact dermatitis (CD) through a double blind, randomized controlled clinical trial in Emam Reza clinic, Shiraz, Iran. Twenty-five patients in each group were randomly assigned to receive whey protein or placebo powder, 30 g in 200 mL warm water at fasting time for 4 weeks. Outcome measures were Dermatology Life Quality Index (DLQI) questionnaire and the Eczema Area and Severity Index (EASI) score. Furthermore, subjective total improvement (assessed by visual analogue scale) was set as the other primary outcome measure. A significant decrease was observed in the scores of EASI, DLQI, and subjective total improvement in the drug group after the intervention compared with the baseline. However, no changes were seen in the placebo group. Moreover, there was a significant reduction in the scores of EASI (P = .002) and subjective total improvement scores (P = .039) over the study period in the drug group compared with the placebo group. According to the results of this study, it seems that oral supplementation of whey protein could improve the symptoms of CD compared with placebo.

In silico prediction of B-cell epitopes for twenty-five mite allergens: The therapeutic potentials for immunotherapy.

Mite allergens are one of the major allergens; however, their structures and epitopes have not been thoroughly studied. In the present study, we predicted the tertiary structures of several mite allergens and also identified the B-cell epitopes, which can be suggested as potential epitopes for allergen immunotherapy. Twenty-five mite allergens, from six mite allergen groups, were investigated; homology modeling and structure refinement were performed for seventeen allergens with unknown structures. Furthermore, various servers were employed to predict linear and conformational B-cell epitopes and consensus B-cell epitopes were identified (172 linear and 64 conformational epitopes). Conservation and epitope identity were also determined among the allergens of the same group and some conserved epitopes were identified. Some regions of the predicted epitopes were identified as novel epitope regions. The predicted consensus epitopes can be applied as suitable candidates to design immunotherapeutic vaccines.

The effect of baked milk on accelerating unheated cow's milk tolerance: A control randomized clinical trial.

BACKGROUND: Assessing the effect of adding baked milk products to the diet of patients with cow's milk allergy on accelerating the formation of tolerance. METHOD: A randomized clinical trial was carried out with 84 patients (6 months-3 years old) diagnosed with allergy to cow's milk who tolerated baked milk in form of muffin in oral food challenge (OFC). The subjects were divided randomly into case and control groups matched for age and sex. Patients in the case group were asked to consume baked milk in the form of muffin for 6 months and then to consume baked cheese in the form of pizza for another 6 months. The control group were instructed to strictly avoid any milk products for 1 year. Skin prick test (SPT) and serum-specific immunoglobulin E (sIgE) levels (ImmunoCAP) of milk, casein, and beta-lactoglobulin were measured before and after the study. In addition, those in the case group who had satisfactorily tolerated baked products during the study as well as all the subjects in the control group underwent an OFC to evaluate unheated milk tolerance at the end of the study. RESULTS: It was shown that by the end of the 1-year study period, 88.1% (37/42) of the patients in the case group and 66.7% (28/42) of those in control group had developed tolerance to unheated milk (P-value: 0.018). The results of milk-specific SPT and sIgE levels showed a significant decrease in the case group. Initial sIgE levels could not predict unheated milk tolerance in case and control groups. CONCLUSION: Introducing baked milk products into the diet of patients with milk allergy can accelerate the tolerance of unheated milk in these patients. sIgE levels of milk, casein, and beta-lactoglobulin did not predict the tolerance of unheated milk.

Evaluation of vitamin D deficiency and low bone mass in children with asthma in fars province: A case-control study.

Background and Aims: Asthma is a chronic inflammatory pulmonary disease which affects 10%-20% of children and adolescents. Inhaled corticosteroids (ICS) is one of its most effective therapies. The effect of systemic corticosteroids on decreasing bone mineral density (BMD) was investigated and proved in children; however, the influence of ICSs on bone density has still remained unclear. This study evaluates the bone mineral density of children and adolescents with asthma in southern Iran and the associated factors, for example, amount of used inhaled steroid. Method: This case-control study enrolled 41 children and adolescents (aged 8-18 years) with asthma and their age and gender-matched controls in 2019-2020. Serum Calcium, phosphate, vitamin D, and bone mineral density were measured. Their physical activity, sun exposure, and fracture history were evaluated subjectively. Results: Lumbar BMD and BMD Z-score in patients showed no significant difference with controls (p = 0.23, p = 0.73). Also, it showed that there was no significant difference in biochemical studies, growth, and bone densitometry parameters between patients who used ICSs for less than 3 months/year corticosteroid therapy compared to those with equal or more than 3 months/year usage. Prevalence of vitamin D deficiency was 28% and 8% in the controls and patients, respectively (p = 0.005). Conclusion: The present study showed that 9.46% of children and adolescents with asthma had low bone mass for chronological age, and it is not significantly higher than normal population. Dosage of inhaled steroid did not associate with osteoporosis in these patients. Prevalence of vitamin D deficiency in patients was lower than normal population, probably due to receiving vitamin D in their routine follow-ups.

Exploring the potential and safety of quantum dots in allergy diagnostics.

Biomedical investigations in nanotherapeutics and nanomedicine have recently intensified in pursuit of new therapies with improved efficacy. Quantum dots (QDs) are promising nanomaterials that possess a wide array of advantageous properties, including electronic properties, optical properties, and engineered biocompatibility under physiological conditions. Due to these characteristics, QDs are mainly used for biomedical labeling and theranostic (therapeutic-diagnostic) agents. QDs can be functionalized with ligands to facilitate their interaction with the immune system, specific IgE, and effector cell receptors. However, undesirable side effects such as hypersensitivity and toxicity may occur, requiring further assessment. This review systematically summarizes the potential uses of QDs in the allergy field. An overview of the definition and development of QDs is provided, along with the applications of QDs in allergy studies, including the detection of allergen-specific IgE (sIgE), food allergens, and sIgE in cellular tests. The potential treatment of allergies with QDs is also described, highlighting the toxicity and biocompatibility of these nanodevices. Finally, we discuss the current findings on the immunotoxicity of QDs. Several favorable points regarding the use of QDs for allergy diagnosis and treatment are noted.

Immune checkpoint molecules in prevention and development of asthma.

Allergic asthma is a respiratory disease initiated by type-2 immune responses characterized by secretion of alarmins, interleukin-4 (IL-4), IL-5, and IL-13, eosinophilic inflammation, and airway hyperresponsiveness (AHR). Immune checkpoints (ICPs) are inhibitory or stimulatory molecules expressed on different immune cells, tumor cells, or other cell types that regulate immune system activation and maintain immune homeostasis. Compelling evidence indicates a key role for ICPs in both the progression and prevention of asthma. There is also evidence of asthma development or exacerbation in some cancer patients receiving ICP therapy. The aim of this review is to provide an updated overview of ICPs and their roles in asthma pathogenesis, and to assess their implications as therapeutic targets in asthma.

Clinical Course, Therapeutic Management and Outcome of Coronavirus Disease in Patients With Inborn Errors of Immunity: A Retrospective Multicenter Experience From Iran.

BACKGROUND: Inborn errors of immunity (IEIs) are characterized by defects in the structure and function of the immune system. This study was designed to assess the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on this potentially particularly susceptible group of patients. METHODS: This retrospective cross-sectional study analyzed patients from 3 referral immunodeficiency centers in Iran. The demographic, clinical, laboratory and therapeutical data of confirmed IEI patients with SARS-CoV-2 infection were collected and analyzed. RESULTS: A total of 19 IEI patients, 52.6% male and 47.4% female, with coronavirus disease 2019 (COVID-19) were enrolled. The most common diagnosed IEIs were (severe) combined immunodeficiency ((S)CID) (9, 47.4%) and predominantly antibody deficiencies (7, 36.8%). The main presenting symptoms included fever (16, 84.2%), cough (12, 63.2%), dyspnea (9, 47.4%) and myalgia (8, 42.1%). Among additional preexisting comorbidities, atopy ( P = 0.087) and renal disorders ( P = 0.087) were more strongly associated with the development of respiratory failure, although not statistically significant. SARS-CoV-2 infection was determined by polymerase chain reaction (n = 19, 100%) within a median (interquartile range) of 1 (0-6) days following admission. Among all laboratory indices, thrombocytopenia ( P = 0.009) was associated with a need for intensive care unit admission. The overall mortality rate was 36.9% and highest among (S)CID patients (4, 44.4%). CONCLUSIONS: Severe COVID-19 most frequently affected (S)CID and predominantly antibody deficiencies patients among this multicenter Iranian cohort. Further studies are required to evaluate the impact of additional preexisting comorbidities and the development of thrombocytopenia on the severity and prognosis of COVID-19 in IEIs.

The Effect of COVID-19 Pandemic on Patients with Primary Immunodeficiency: A Cohort Study.

Both adaptive and innate immune responses are essential for an effective defense against the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection. We aimed to investigate the effect of the coronavirus disease 2019 (COVID-19) pandemic on patients with primary immunodeficiency (PID). This study was performed on patients who were diagnosed with PID by immunologist specialists and referred to Imam Reza Clinic of Asthma and Allergy, affiliated with Shiraz University of Medical Sciences, (Shiraz, Iran) for regular check-ups. The patients were enrolled in this cohort study and followed for any sign of COVID-19 from March 2020 to May 2021. COVID-19 infection was confirmed using a real-time polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Among the 90 PID patients under study, nine patients (10%) were diagnosed positive for COVID-19 infection. Five out of these nine patients belonged to the combined immunodeficiency (CID) category, while four patients were categorized as having primary antibody deficiencies (PADs). Eight patients with COVID-19 were required to be admitted to the hospital, and three patients died after hospitalization due to COVID-19 infection. It seems that patients with CID are at a higher risk of mortality, due to COVID-19 infection, that other types of PID.

An Update on Protective Effectiveness of Immune Responses After Recovery From COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits variable immunity responses among hosts based on symptom severity. Whether immunity in recovered individuals is effective for avoiding reinfection is poorly understood. Determination of immune memory status against SARS-CoV-2 helps identify reinfection risk and vaccine efficacy. Hence, after recovery from COVID-19, evaluation of protective effectiveness and durable immunity of prior disease could be significant. Recent reports described the dynamics of SARS-CoV-2 -specific humoral and cellular responses for more than six months in convalescent SARS-CoV-2 individuals. Given the current evidence, NK cell subpopulations, especially the memory-like NK cell subset, indicate a significant role in determining COVID-19 severity. Still, the information on the long-term NK cell immunity conferred by SARS-CoV-2 infection is scant. The evidence from vaccine clinical trials and observational studies indicates that hybrid natural/vaccine immunity to SARS-CoV-2 seems to be notably potent protection. We suggested the combination of plasma therapy from recovered donors and vaccination could be effective. This focused review aims to update the current information regarding immune correlates of COVID-19 recovery to understand better the probability of reinfection in COVID-19 infected cases that may serve as guides for ongoing vaccine strategy improvement.

An unusual case of cystic fibrosis with pancytopenia due to copper deficiency and blindness caused by vitamin A deficiency: A case-report.

Cystic fibrosis (CF) is a multi-systemic autosomal recessive disease which mostly involves the respiratory, digestive, and reproductive systems, but it can present with various clinical presentations, especially in adulthood. We describe a 19-year-old boy, a known case of CF who presented with less known clinical presentations of CF, blindness, liver cirrhosis, vitamin A deficiency, and pancytopenia.

A rare case of SRD5A3-CDG in a patient with ataxia and telangiectasia: A case report.

Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is an extremely rare congenital disease. Common manifestations are developmental delay, intellectual disability, ophthalmological abnormalities, cerebellar abnormalities, ataxia, and hypotonia. Here, we discuss a seven-year-old boy with SRD5A3-CDG (homozygous variant c.57G>A [p.Trp19Ter]), featuring the unprecedented finding of telangiectasia.

Homozygous Autosomal Recessive DIAPH1 Mutation Associated with Central Nervous System Involvement and Aspergillosis: A Rare Case.

The DIAPH1 gene fulfills critical immune and neurodevelopmental roles. It encodes the mammalian Diaphanous-related formin (mDia1) protein, which acts downstream of Rho GTPases to promote F-actin polymerization and stabilize microtubules. During mitosis, this protein is expressed in human neuronal precursor cells and considerably affects spindle formation and cell division. In humans, dominant gain-of-function DIAPH1 variants cause sensorineural deafness and macrothrombocytopenia (DFNA1), while homozygous DIAPH1 loss leads to seizures, cortical blindness, and microcephaly syndrome (SCBMS). To date, only 16 patients with SCBMS have been reported, none of whom were from Iran. Furthermore, aspergillosis is yet to be reported in patients with homozygous DIAPH1 loss, and the link between SCBMS and immunodeficiency remains elusive. In this study, we shed further light on this matter by reporting the clinical, genetic, and phenotypic characteristics of an Iranian boy with a long history of recurrent infections, diagnosed with SCBMS and immunodeficiency (NM_005219.5 c.3145C > T; p.R1049X variant) following aspergillosis and SARS-CoV-2 coinfection.