A Novel Disease-Causing ASPA Gene Mutation (c.432+1 G>C) in an Iranian Patient with Canavan Disease: A Case Report

Canavan disease is an autosomal recessive genetic disease and rare fatal childhood neurological disorder caused by mutations in the ASPA gene, which resulted in a catalytic deficiency of the ASPA enzyme that catalyzes the hydrolysis of NAA into aspartate and acetate. Herein, we report an Iranian patient diagnosed with Canavan disease with a novel splice-site mutation in the ASPA gene (NM_000049.4; c.432+1 G>C). This report is based on a homozygous c.432+1 G>C mutation in the ASPA gene identified from an Iranian patient. As a result, a novel homozygous pathogenic mutation on ASPA is the cause of disease in the patient.

Severe phenotype of an Iranian patient with methemoglobinemia type II due to a novel mutation in the CYB5R3 gene

Methemoglobinemia is a rare autosomal recessive genetic disease caused by disruptive mutations in the CYB5R3 gene (MIM: 250800). Herein, a novel mutation is reported in an Iranian patient affected with methemoglobinemia type II. In this case study, the patient is precisely described according to the thoroughly carried-out examinations and workups. In so doing, the peripheral blood sample was collected to evaluate the methemoglobin level and NADH-CYB5R3 activity test. Moreover, whole-exome sequencing (WES) was recruited to identify the mutation leading to this disorder. Subsequently, Sanger sequencing was employed to confirm the detected mutation. Magnetic Resonance Imaging was also performed to explore the structure of the brain. As identified by the blood test, the methemoglobin level increased up to 25%, and the NADH-CYB5R3 enzyme activity showed to be 13.8 IU/g of Hb. A novel homozygous mutation in CYB5R3 (NM_001171661: g.23435C>T, c.181C>T, p.R61X, rs1210302322) was identified as the cause of the Methemoglobinemia type II in the proband. This nonsense mutation alters arginine to the stop codon at position 61 of protein in the FAD-binding domain that results in a truncated protein. The MRI revealed brain atrophy and corpus calusom hypoplasticity. It was established that this variation can lead to Methemoglobinemia. The proband demonstrates Methemoglobinemia type II phenotype such as cyanosis, severe mental retardation, microcephaly, as well as developmental delay. The brain MRI revealed brain atrophy and corpus calusom hypoplasticity. The cyanosis symptom is managed by daily ascorbic acid uptake.

A Novel Variant in Iranian Patient with Cystinuria: A Case Report

Cystinuria is an autosomal recessive disorder in which the renal reabsorption of cystine, arginine, lysine and ornithine are disturbed. The two genes, the pathogenic forms of which are responsible for the disorder, are SLC7A9 and SLC3A1. In this study, we describe a disease that has a new c.916A> T variant (p. K306 *) in exon 5 of the SLC3A1 gene. This variant results in the NMD phenomenon in which the protein product is not produced because of mRNA destruction. In 2020, blood sample of a 41-yr-old man from east Azerbaijan, Iran together with his parents were collected to be studied. PCR and direct sequencing were performed to detect the possible SLC3A1 variant. Whole-gene sequence analysis done by Mutation surveyor Software revealed a novel nonsense homozygous variant in exon 5 of the gene. Parental Sequence Analysis shows that they are heterozygous. According to ACMG guideline, this variant is considered as pathogen. Finding serious mutations can allow rapid screening for cystinuria by analyzing common mutations. It should also be considered as a pathogenic variant in patients’ cystinuria.

A novel frameshift pathogenic variant in ST3GAL5 causing salt and pepper developmental regression syndrome (SPDRS): A case report

GM3 synthase deficiency is associated with salt and pepper developmental regression syndrome (SPDRS), a rare genetic disorder. Herein, we report the first Iranian patient with SPDRS. We detected a novel pathogenic variant of ST3GAL5 (NM_003896.4: c.1030_1031del, p.Ile344Cysfs*11). The proband had intellectual disability (ID), failure to thrive, cerebral atrophy, microcephaly, and atonic seizures. The main future challenge proceeding from the results of this study is the prenatal detection of the newly discovered variant; the next step would involve further studies to elucidate the phenotypic spectrum of SPDRS and detect new variants that could cause symptoms ranging from mild to severe.

Vulvar Pyogenic Granuloma in Adult Female Population: A Case Report and Review of the Literature

Pyogenic granuloma (PG) is an uncommon lesion of unknown etiology. It may be formed following a minor injury. They result from a reactive or inflammatory process consisting of proliferating vascular channels, immature fibroblastic connective tissue, and scattered inflammatory cells rather than neoplastic process. Bleeding is the most common symptom of the lesion. They may be seen in all age groups, and there is no clear predominance of a gender. Vulvar PGs can be confused with other polypoid or sessile lesions of the genital site. There are only a few cases of female genital PGs reported in the literature. Herein, we describe the first case of vulvar (clitoral) PG in an Iranian patient and a brief review of the literature in this regard.

Molecular Genetic Study of Congenital Ichthyosiform Erythroderma (CIE) Reveals a Novel Likely Pathogenic Variant in an Iranian Pedigree

Introduction: Congenital ichthyosiform erythroderma (CIE) is a subtype of autosomal recessive congenital ichthyosis (ARCI), a group of ineffective keratinization disorders, which mainly results from missense mutations in the transglutaminase 1 (TGM1) gene. Case Presentation: Herein, a 9-year-old male case of CIE is presented, for whom we conducted genetic testing to uncover the underlying molecular cause of his condition. We performed whole-exome sequencing (WES) on the DNA extracted from blood, and the data was analyzed for checking pathogenic variants. Analysis of the WES data identified a novel missense variant, c.1165C >T (p. Arg389Cys), in the TGM1 gene. Evaluation of this variant via in silico tools showed its detrimental consequences on the stability and function of the encoded protein. The variant was characterized as likely pathogenic based on the American College of Medical Genetics and Genomics guidelines for variant interpretation. Analysis of all available family members confirmed the co-segregation of this novel variant with the CIE disease within the family. Conclusions: This study reported the successful application of WES and bioinformatics analysis to identify a novel mutation in a well-established ARCI-causing residue in an Iranian patient.

A novel PTRH2 missense mutation causing IMNEPD: a case report

PTRH2 deficiency is associated with an extremely rare disease, infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). We report the first Iranian patient with IMNEPD. We detected a pathogenic variant in the PTRH2 gene (NM_016077.5: c.68T > C, p.V23A). The proband has myopia, spastic diplegic cerebral palsy, urolithiasis, and a history of seizures.