Is Bax/Bcl-2 ratio considered as a prognostic marker with age and tumor location in colorectal cancer?

Bax and Bcl-2 are the major members of Bcl-2 family whose play a key role in tumor progression or inhibition of intrinsic apoptotic pathway triggered by mitochondrial dysfunction. Therefore, the balance between pro- and anti-apoptotic members of this family can determine the cellular fate. In this study, the relative level of mRNA expression of Bax and Bcl-2 genes was determined using RNA extraction, cDNA synthesis and RT-qPCR technique from 22 tumoral tissues and adjacent non-tumoral tissues from adenocarcinoma colorectal cancer. The potential prognostic and predictive significance of Bax and Bcl-2 gene expression and Bax/Bcl-2 ratio were demonstrated in colorectal cancer. The significant correlation between qPCR data and different clinicopathologic parameters of colorectal carcinoma, including age, gender, tumor size, tumor stage, tumor location, and tumor differentiation was also examined. Interestingly, no significant correlation was seen between Bax and Bcl-2 expressions and clinicopathological parameters of colorectal cancer. However, Bax/Bcl-2 ratio was statistically correlated with age and tumor location. Patients with age above 50 showed decreased levels of Bax/Bcl-2 ratio. Moreover, the Bax/Bcl-2 ratio was significantly lower in tumors resected from colon compared to sigmoid colon, rectosigmoid and rectum tumors. This study indicates a significant correlation between age and tumor location with Bax/Bcl-2 expression ratio, suggesting predictive value as a potential molecular marker of colorectal cancer

Three novel mutations in Iranian patients with Tay-Sachs disease

Tay-Sachs disease [TSD], or GM2 gangliosidosis, is a lethal autosomal recessive neurodegenerative disorder, which is caused by a deficiency of beta-hexosaminidase A [HEXA], resulting in lysosomal accumulation of GM2 ganglioside. The aim of this study was to identify the TSD-causing mutations in an Iranian population. In this study, we examined 31 patients for TSD-causing mutations using PCR, followed by restriction enzyme digestion. Molecular genetics analysis of DNA from 23 patients of TSD revealed mutations that has been previously reported, including four-base duplications c.1274_1277dupTATC in exon 11 and IVS2+1G>A, deletion TTAGGCAAGGGC in exon 10 as well as a few novel mutations, including C331G, which altered Gln>Glu in HEXB, A>G, T>C, and p.R510X in exon 14, which predicted a termination codon or nonsense mutation. In conclusion, with the discovery of these novel mutations, the genotypic spectrum of Iranian patients with TSD disease has been extended and could facilitate definition of disease-related mutations

Molecular and clinical investigation of Iranian patients with Friedreich ataxia

Friedreich ataxia [FRDA] is an autosomal recessive disorder caused by guanine-adenine-adenine [GAA] triplet expansions in the FXN gene. Its product, frataxin, which severely reduces in FRDA patients, leads to oxidative damage in mitochondria. The purpose of this study was to evaluate the triple nucleotide repeated expansions in Iranian FRDA patients and to elucidate distinguishable FRDA clinical differences in these patients. A number of 22 Iranian patients [8 females and 14 males] from 16 unrelated families were studied. DNA was extracted from the peripheral blood of patients. The frequency and length of [GAA]n repeats in intron 1 of the FXN gene were analyzed using long-range PCR. In this study, the clinical criteria of FRDA in our patients and the variability in their clinical signs were also demonstrated. An inverse relationship was observed between GAA repeat size and the age of onset. Although some distinguishable clinical features [such as limb ataxia and lower limb areflexia] were found in our patients, 90-95% of them had extensor plantar response and dysarthria. The results showed only one positive diabetes patient and also different effects on eye movement abnormality among our patients. The onset age of symptoms showed a significant inverse correlation with allele size in our patients [P>0.05]. Based on comparisons of the clinical data of all patients, clinical presentation of FRDA in Iranian patients did not differ significantly from other FRDA patients previously reported

Identification of a novel arylsulfatase b gene mutation in three unrelated Iranian mucopolysaccharidosis type-vi patients with different phenotype severity

Mucopolysaccharidosis type-VI [MPS-VI], which is inherited as an autosomal recessive trait, results from the deficiency of N-acetylgalactosamine 4-sulfatase [arylsulfatase B] activity and the lysosomal accumulation of dermatan sulfate. In this study, ARSB mutation analysis was performed on three unrelated patients who were originally from the West Azerbaijan province of Iran. After PCR and direct DNA sequencing, DNA extraction was performed. Sequencing analysis revealed a novel homozygous missense mutation in the ARSB gene at c. 457A>G [p. D486V] in three unrelated Iranian MPS-VI patients with different phenotype severity. The mutation type in three patients was the same; probably, because of a foundation effect on their population

novel mutation in the aprataxin [APTX] gene in an Iranian individual suffering early-onset ataxia with oculomotor apraxia type 1[AOA1] disease

Ataxia with oculomotor apraxia type 1 [AOA1] shows early onset with autosomal recessive inheritance and is caused by a mutation in the aprataxin [APTX] gene encoding for the APTX protein. In this study, a 7-year-old girl born of a first-cousin consanguineous marriage was described with early-onset progressive ataxia and AOA, with increased cholesterol concentration and decreased albumin concentration in serum. PCR and direct DNA sequencing was performed after DNA extraction. Sequencing analysis revealed a novel homozygous deletion in c.643 and A>T single nucleotide polymorphism in c.641 in exon 6 of the APTX gene [ENST00000379825]. It seems that this region of exon 6 is probably a hot spot; however, no deletions have been reported in exon 6 yet