Gene, Cell and Tissue
Volume:3 Issue: 1, Jan 2016

Deficient lysosomal α-galactosidase activity leads to intracellular accumulation of globotriaosylceramide (Gb3), which is the pathologic hallmark of Fabry disease (FD). There are over 750 pathogenic variants identified in the α-galactosidase gene (GLA). In rare patients, the cause of α-galactosidase deficiency is the overexpression of a GLA transcript with a cryptic exon in intron 4, which is physiologically present at trace levels.
We aim to report abnormally spliced alpha-galactosidase mRNA transcripts found with a cDNA-based GLA genotyping protocol performed in 482 patients.
Patients and Genomic DNA and total RNA specimens were obtained from peripheral blood leukocytes of patients with premature stroke prospectively enrolled in the PORTYSTROKE study, or of patients with possible clinical manifestations of FD who have been referred for molecular diagnostic workup.
Approximately 20% of the patients expressed alternatively spliced transcripts of GLA mRNA involving exon 3. We additionally report that such non-canonical transcripts are physiologically expressed at trace levels in healthy individuals, and that their expression in leukocytes markedly increased in blood samples kept at room-temperature for 48 hours before RNA extraction.
Production of alternatively spliced GLA transcripts might be involved in the regulation of GLA gene expression, and its deregulated overexpression, particularly if restricted to specific cells or tissues, might be the cause of organ-limited Gb3 pathology. Elucidation of the molecular mechanisms underlying the production of the non-canonical GLA transcripts warrants further investigation, as it may contribute important new data to the understanding of the molecular pathology of FD and Gb3-related disorders.

Recurrent pregnancy loss (RPL) is two or more consecutive pregnancy losses before 20 weeks of gestation. So far the disease is known for a variety of reasons, but still about 50% of recurrent pregnancy losses are unknown. The miRNAs are a family of 20 - 25 nucleotide RNA that inhibit translation of the target gene or mRNA degradation and play a key role in a variety of regulatory pathways. The miRNA is involved in embryonic developments and regulatory disorders which cause numerous diseases including heart diseases and pregnancy-associated disorders. Recent studies suggest that common genetic factors may exist between ischemic heart disease and abortion.
The current study aimed to investigate the relationship between rs6492538 polymorphism of MIR17HG gene and recurrent spontaneous abortion, which might be clinically useful as a marker to assess risks for recurrent pregnancy loss to provide good health care during pregnancy.
The case and control groups were studied for the association between polymorphism of MIR17HG and recurrent pregnancy loss in Iranian females. One-hundred patients with recurrent abortions (at least two) as cases and one-hundred healthy female with two or more normal term deliveries and without a history of abortion were selected as controls. Total genomic DNA was isolated from blood leukocytes. SNPs were studied with Alu1 as a restriction enzyme.
Results of the present study indicated significant association between rs6492538 polymorphism and recurrent pregnancy loss (P > 0.05).
The results of the present study provide evidence for association between genetic variation in MIR17HG and recurrent spontaneous abortion. Further studies will be required to validate the significance of the studied genetic variation in diverse populations and its regulatory role on target genes.

Cerebral ischemia and reperfusion (I/R) is a pathological condition that arises by reduction or cessation in cerebral blood flow and return of oxygen and metabolites to brain cells, which cause oxidative damage.
The aim of this study was to investigate the neuroprotective effects of Withania coagulans (WC) extract on brain cortex in a rat model of I/R.
Thirty-two adult male Wistar rats weighing 280 - 300 g were used in this study. Animals were randomly divided to four groups (n = 8) as follow: sham operated group (I), I/R group (II), WCE500 I/R (III) and WCE1000 I/R groups (IV). Pretreatment with WC extract (500, 1000 mg/kg) was done by oral gavage for 30 days and global brain ischemia was induced by the common carotid occlusion for 30 minutes. After 72 hours, the animals were perfused transcardially and then the brains were prepared for histological study (H & E and TUNEL staining).
The I/R group showed a significant increase in pycnotic (dying) neurons and pretreatment with WC at doses of 500 mg/kg and 1000 mg/kg significantly reduced pycnotic and TUNEL positive neurons, in a dose dependent manner in ischemic brain cortex.
Our findings indicated that WC has neuroprotective effects and is able to reduce histopathological alterations and apoptosis in brain cortex I/R in rats.

Myofibrillar myopathy (MFM) is a rare human disease, characterized by a distinct histopathological pattern of myofibrillar degeneration and protein aggregates. LDB3 protein encoded by this gene is a key Z-disk protein that interacts with α-actinin and protein kinase C..
In this paper, we identified the novel heterozygous, and hence, dominant mutation in the LIM domain-binding protein 3 gene (LDB3) in a patient affected by myofibrillar myopathy (MFM). We performed direct sequencing in an Iranian patient with autosomal-dominant inheritance of MFM characterized by clinical features, and we identified a heterozygous missense mutation in exon 10, c.1687A > G (p.Ile563Val) in the LDB3 gene on chromosome 10:88476524.
Bioinformatics analyses using SIFT, Mutation Taster and Polyphen-2 indicated that p.Ile563Val was predicted to be damaging, disease causing, and probably damaging to and causing LDB3 dysfunction. As such, this mutation produces novel protein coding transcripts, which might explain the MFM phenotype in the patient.

Oculocutaneous albinism (OCA) is a genetically heterogeneous autosomal recessive genetic disorder that is characterized by reduced or completely absent pigmentation in the hair, skin, and eyes.
In the present study, in order to verify OCA type 1A in a patient with clinical symptoms, and to study the variations of the TYR gene for the first time in southwest Iran, this gene was entirely sequenced.
A novel homozygous mutation, the deletion of exons 1 - 5 on the TYR gene, was found on the molecular genetic testing of this patient. Exon 1 - 5 deletion on TYR causes a lack of the tyrosinase enzyme and disturbs the melanin biosynthesis process..