Revisiting double-negative T cells in autoimmune lymphoproliferative immunodeficiencies: a case series.

Background: Elevated level of double-negative T (DNT) cells is a historical hallmark of autoimmune lymphoproliferative syndrome (ALPS) diagnosis. However, the peripheral blood level of DNT cells might also be compromised in autoimmune lymphoproliferative immunodeficiencies (ALPID) other than ALPS, inattention to which would increase the delay in diagnosis of the underlying genetic defect and hinder disease-specific treatment.

Materials And Methods: This cross-sectional study recruited patients suffering from ALPID (exclusion of ALPS) with established genetic diagnosis.

Aicardi-Goutières Syndrome Type 1: A Novel Missense Variant and Review of the Mutational Spectrum.

Objectives: Mutations in the TREX1 gene cause Aicardi-Goutières syndrome (AGS) 1, associated with a spectrum of autoimmune and neurodegenerative manifestations. AGS 1, the most severe neonatal type of AGS, is characterized by abnormal neurologic findings, visual inattention, hepatosplenomegaly, thrombocytopenia, skin rash, restlessness, and fever.

Materials & Methods: The present study described two affected siblings from an Iranian family whose phenotypes overlap with intrauterine infections.

Distinct neurological phenotypes associated with biallelic loss of NOTCH3 function: evidence for recessive inheritance.

Background: NOTCH3 variants are known to be linked to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, some null NOTCH3 variants with homozygous inheritance cause neurological symptoms distinct from CADASIL. The aim of this study was to expand the clinical spectrum of this distinct condition and provide further evidence of its autosomal recessive inheritance.

A novel missense variant in identified in a consanguineous Iranian family with vanishing white matter disease and a brief review of the literature.

Vanishing of white matter (VWM) is a hereditary heterogeneous brain disorder that most often affects children. However, the onset of the disease varies from childhood to adulthood. VWM is caused by mutations in one of the five genes encoding subunits of the eukaryotic initiation factor eIF2B.

Clinical, Immunological, and Genetic Findings in Iranian Patients with MHC-II Deficiency: Confirmation of c.162delG RFXANK Founder Mutation in the Iranian Population.

Purpose: Major histocompatibility complex class II (MHC-II) deficiency is a rare inborn error of immunity (IEI). Impaired antigen presentation to CD4 + T cells results in combined immunodeficiency (CID). Patients typically present with severe respiratory and gastrointestinal tract infections at early ages.

A Novel Mutation in the OXCT1 Gene Causing Succinyl-CoA:3-Ketoacid CoA Transferase (SCOT) Deficiency Starting with Neurologic Manifestations.

Succinyl-CoA:3-oxoacid CoA-transferase (SCOT) deficiency is an inborn error of ketone body utilization characterized by intermittent ketoacidosis crises. This study reports the first Iranian patient with SCOT deficiency who presented with seizure and hypotonia at birth. Accordingly, she was consequently re-hospitalized due to hypotonia and respiratory distress.

A rare immunological disease, caspase 8 deficiency: case report and literature review.

Background: Caspase-8 is a molecule in the FAS pathway that initiates apoptosis. One of the rarest autoimmune lymphoproliferative syndromes is caspase-8 deficiency. Immunodeficiency, splenomegaly, and lymphadenopathy are the common symptoms of this condition.

New Presentation of CD27 Deficiency; Coronary Ectasia and COVID-19.

CD27 is a costimulatory receptor involved in the maturation of the innate and adaptive immunity. CD27, through interaction with CD70, plays a role in the control of Epstein-Barr virus (EBV) infection. CD27 deficiency leads to an immune dysregulation disease characterized by EBV susceptibility.

Intestinal hypomagnesemia in an Iranian patient with a novel TRPM6 variant: a case report and review of the literature.

TRPM6 is predominantly expressed in the kidney and colon and encodes a protein containing an ion channel domain and a protein kinase domain. It is crucial for magnesium homeostasis and plays important roles in epithelial magnesium transport and the active magnesium absorption. In this study, we present a 70-day-old Iranian female patient from consanguineous parents with hypomagnesemia and secondary hypocalcemia.

Novel PGM3 mutation in two siblings with combined immunodeficiency and childhood bullous pemphigoid: a case report and review of the literature.

Background: Bullous pemphigoid is the most common autoimmune subepidermal blistering disorder with a low incidence in childhood. Combined immunodeficiencies (CIDs) are a group of monogenic inborn errors of immunity (IEIs) characterized by T- and B-cell dysfunction leading to recurrent infections, lymphoproliferation, predisposition to malignancy, and autoimmunity. Here, we report two Afghan siblings with a diagnosis of CID and extremely rare manifestation of diffuse bullous pemphigoid skin lesions.

Integrated genomic sequencing in myeloid blast crisis chronic myeloid leukemia (MBC-CML), identified potentially important findings in the context of leukemogenesis model.

Chronic myeloid leukemia (CML) is a model of leukemogenesis in which the exact molecular mechanisms underlying blast crisis still remained unexplored. The current study identified multiple common and rare important findings in myeloid blast crisis CML (MBC-CML) using integrated genomic sequencing, covering all classes of genes implicated in the leukemogenesis model. Integrated genomic sequencing via Whole Exome Sequencing (WES), Chromosome-seq and RNA-sequencing were conducted on the peripheral blood samples of three CML patients in the myeloid blast crisis.

Next-generation sequencing identified novel truncating mutations in BBS9 causing Bardet Biedl syndrome in two Iranian consanguineous families.

Objectives: Bardet-Biedl syndrome (BBS) is an autosomal recessive pleiotropic ciliopathy, which includes multi-organ clinical manifestations. The known genes involved in the development of the disease account for the causality in about 80% of the examined cases.

Materials & Methods: We investigated two Iranian unrelated clinically diagnosed BBS patients, using a targeted next-generation sequencing panel consisting of 18 known BBS genes.

X-linked SCID with a rare mutation.

Background: Severe combined immunodeficiency (SCID) is a group of relatively rare primary immunodeficiency disorders (PIDs), characterized by disturbed development of T cells and B cells, caused by several genetic mutations that bring on different clinical presentations. SCID may be inherited as an autosomal recessive or an X-linked genetic trait.

Case Presentation: A 6-year-old male presented with a history of food allergy, productive coughs, and recurrent purulent rhinitis, poor weight gain and hypothyroidism.

Whole-Exome Sequencing Identified a Novel Variant (C.405_422+39del) in Gene in an Iranian Pedigree with Familial Dilated Cardiomyopathy.

Background: Dilated cardiomyopathy (DCM) is a progressive heart condition characterized by left ventricular chamber enlargement associated with systolic heart failure and prolonged action potential duration. Genetic variations in genes that encode cytoskeleton, sarcomere, and nuclear envelope proteins are responsible for 45% of cases. In our study, we focused on a pedigree with familial DCM to decipher the potential genetic cause(s) in affected members developing arrhythmia, end-stage heart failure, and sudden death.

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.

Identification of a novel truncating variant in AHI1 gene and a brief review on mutations spectrum.

Joubert syndrome (JS) is a rare inherited neurodevelopmental condition characterized by hypotonia, ataxia, developmental delay, abnormal eye movements, neonatal respiratory disturbance and unique midbrain-hindbrain malformation, known as the molar tooth sign. JS is a genetically heterogeneous disorder with nearly 35 ciliary genes are implicated in its pathogenesis. AHI1 gene is one of the most frequently mutated gene in JS patients which is accounted for 8-11% of cases, particularly in Arab population.

Exome sequencing reveals novel rare variants in Iranian familial multiple sclerosis: The importance of POLD2 in the disease pathogenesis.

The prevalence of familial multiple sclerosis (FMS) is increasing worldwide which endorses the heritability of the disease. Given that many genome variations are ethnicity-specific and consanguineous marriage could affect genetic diseases, hereditary disease gene analysis among FMS patients from Iran, a country with high rates of parental consanguinity, could be highly effective in finding mutations underlying disease pathogenesis. To examine rare genetic mutations, we selected three Iranian FMS cases with ≥3 MS patients in more than one generation and performed whole exome sequencing.

The importance of CDC27 in cancer: molecular pathology and clinical aspects.

Background: CDC27 is one of the core components of Anaphase Promoting complex/cyclosome. The main role of this protein is defined at cellular division to control cell cycle transitions. Here we review the molecular aspects that may affect CDC27 regulation from cell cycle and mitosis to cancer pathogenesis and prognosis.

Four mutations in MITF, SOX10 and PAX3 genes were identified as genetic causes of waardenburg syndrome in four unrelated Iranian patients: case report.

Background: Waardenburg syndrome (WS) is a rare genetic disorder. The purpose of this study was to investigate clinical and molecular characteristics of WS in four probands from four different Iranian families.

Case Presentation: The first patient was a 1-year-old symptomatic boy with congenital hearing loss and heterochromia iridis with a blue segment in his left iris.

SPOAN syndrome: a novel mutation and new ocular findings; a case report.

Background: To report a novel mutation and new clinical findings in a case with SPOAN syndrome (spastic paraplegia, optic atrophy, neuropathy).

Case Presentation: Clinical examination, genetic testing and electroretinography were used to study a 2-year-old child who was referred to our clinic with no visual attention and documented SPOAN syndrome. Fundoscopy revealed optic atrophy, diffuse retinal pigment mottling, severe vascular attenuation, and completely non-vascularized peripheral retina in both eyes.

Succinate Dehydrogenase Deficiency: A Treatable Neurometabolic Disorder.

Succinate dehydrogenase (SDH) deficiency is a rare autosomal recessive neurometabolic disorder that causes brain insult, neurodevelopmental delay, exercise intolerance, and cardiomyopathy. A 25-month-old boy was referred to our neurometabolic center due to developmental regression after injecting the influenza vaccine when he was 10 months old. Magnetic resonance imaging (MRI) showed high signal changes in the brain white matter, and magnetic resonance spectroscopy (MRS) detected a high succinate peak at 2.

Whole Exome Sequencing Reveals a XPNPEP3 Novel Mutation Causing Nephronophthisis in a Pediatric Patient.

Background: Nephronophthisis (NPHP) is a progressive tubulointestinal kidney condition that demonstrates an AR inheritance pattern. Up to now, more than 20 various genes have been detected for NPHP, with NPHP1 as the first one detected. X-prolyl aminopeptidase 3 (XPNPEP3) mutation is related to NPHP-like 1 nephropathy and late onset NPHP.