ALDH1A3-related congenital microphthalmia-8 due to a novel frameshift variant.

Microphthalmia (MCOP) is a group of rare developmental malformations of eye with often reduced size of the eyeball, leading to blindness. Affecting about 1 in 7000 live births, MCOP can occur due to either environmental or genetic factors. Isolated microphthalmia-8 (MCOP8) has been proved to be caused by autosomal recessive mutations of the ALDH1A3 gene (MIM*600463) encoding aldehyde dehydrogenase 1 family, member A3. Herein, we report an 8-year-old boy with vision problems since birth from a first-cousin consanguineous parents. The main symptoms of the patient included severe bilateral microphthalmia, cyst in the left eye and blindness. The child developed behavioral disorders at the age of 7. It should be noted that there is no family history of the disease. To identify the genetic factor underlying the pathogenesis in this case Whole Exome Sequencing (WES) was performed and followed by Sanger sequencing. A novel pathogenic variant, c.1441delA (p.M482Cfs*8), in the ALDH1A3 gene was detected by WES in the proband. Further prenatal diagnosis is highly suggested to the family for the future pregnancies.

SARS-COV-2 RBD (Receptor binding domain) mutations and variants (A sectional-analytical study).

An essential step in SARS-CoV-2 infection is binding the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to the ACE2 receptor on the surface of host cells. Therefore, variation in this region can have crucial effects on clinical outcomes and the emergence of variants of concern (VOCs) and variants of interest (VOIs). In this cross-sectional descriptive study, 54 patients with SARS-COV-2 infection were enrolled. After collecting samples and identifying the virus using the One-Step Real-Time qRT-PCR technique and confirming the viral infection, the region containing the RBD region for detection of any mutations was amplified using the Nested-PCR method. Finally, to identify probable mutations, the Nested-PCR product was sequenced. Our data show that the most mutant strains in circulation in our population are the delta variant (90.74%), alpha variant (5.56%), and omicron variant (3.70%), respectively. Pangolin Lineages strains were B.1.1.7(Alpha variant), B.1.617.2(Delta variant) and B.1.1.529(Omicron variant). Also, the mutation profile of variants suggests that N501Y, T478K, and D614G amino acid substitutions, are the significant mutations in the alpha and delta variants that are common with the Omicron variant. The highest frequency of clinical signs in the patients were: lung involvement (42.59%); fever, chills (40.74%); body pain (15%), and other signs (1.67%). Our data revealed that SARS-COV-2 RBD region variation results in substituting essential amino acids and the emergence of the new variant. We can consider it as a predictor for monitoring the emergence of variants of concerns and viral outcomes.

Identification of a novel mutation in the APTX gene associated with ataxia-oculomotor apraxia.

Hereditary ataxias are a clinically and genetically heterogeneous family of disorders defined by the inability to control gait and muscle coordination. Given the nonspecific symptoms of many hereditary ataxias, precise diagnosis relies on molecular genetic testing. To this end, we conducted whole-exome sequencing (WES) on a large consanguineous Iranian family with hereditary ataxia and oculomotor apraxia. WES in five affected and six unaffected individuals resulted in the identification of a homozygous novel stop-gain mutation in the APTX gene (c.739A>T; p.Lys247*) that segregates with the phenotype. Mutations in the APTX (OMIM 606350) gene are associated with ataxia with oculomotor apraxia type 1 (OMIM 208920).

PTRHD1 (C2orf79) mutations lead to autosomal-recessive intellectual disability and parkinsonism.

INTRODUCTION: Atypical parkinsonism is a neurodegenerative disease that includes diverse neurological and psychiatric manifestations. OBJECTIVES: We aimed to identify the disease-cauisng mutations in a consanguineous family featuring intellectual disability and parkinsonism. METHODS: Full phenotypic characterization, followed by genome-wide single-nucleotide polymorphism genotyping and whole-genome sequencing, was carried out in all available family members. RESULTS: The chromosome, 2p23.3, was identified as the disease-associated locus, and a homozygous PTRHD1 mutation (c.157C>T) was then established as the disease-causing mutation. The pathogenicity of this PTRHD1 mutation was supported by its segregation with the disease status, its location in a functional domain of the encoding protein, as well as its absence in public databases and ethnicity-matched control chromosomes. CONCLUSION: Given the role of 2p23 locus in patients with intellectual disability and the previously reported PTRHD1 mutation (c.155G>A) in patients with parkinsonism and cognitive dysfunction, we concluded that the PTRHD1 mutation identified in this study is likely to be responsible for the phenotypic features of the family under consideration. © 2016 International Parkinson and Movement Disorder Society.

A Single Nucleotide Polymorphism in the FOXP3 Gene Associated with Behçet's Disease in an Iranian Population.

UNLABELLED: Background: Behçet's Disease (BD) is a rare autoimmune disease that involves the dysfunction of regulatory T cells. FOXP3 is a key transcription factor in the development and function of T(reg) cells. Recent studies have shown SNPs in the FOXP3 contribute to the susceptibility to some autoimmune disorders. METHODS: To clarify the association between the FOXP3 gene and the risk of BD, 50 patients diagnosed with BD and 50 healthy controls from north-western Iran were genotyped by PCR-RFLP (Mun I and Pst I) for two SNPs including rs3761547 (-3499T/C) and rs3761548 (-3279 C/A) in the promoter region of the FOXP3 gene. In addition, a 506 bp nucleotide sequence of FOXP3 promoter was analyzed. RESULTS: The allele -3279 C/A was significantly associated with BD [p = 0.002; odds ratio (OR) = 3.841; 95% confidence interval (CI) 1.610 - 9.161]; whereas, there was no contribution of the FOXP3 polymorphism -3499T/C to BD [(p = 0.084); (OR = 0.348, 95% CI = 0.101 - 1.195)]. Meanwhile, sequence analysis showed 100% similarity in both controls and BD patient groups. CONCLUSIONS: Therefore, the SNP rs3761548 in the FOXP3 gene appears to contribute to the risk of Behçet's disease among the north-western Iranian population.