A novel mutation in the SERAC1 gene correlates with the severe manifestation of the MEGDEL phenotype, as revealed by whole-exome sequencing.

The condition 3-methylglutaconic aciduria (3-MGA) with deafness, encephalopathy and Leigh-like (MEGDEL) syndrome, also known as 3-MGA IV, is one of a group of five rare metabolic disorders characterized by mitochondrial dysfunction, resulting in a series of phenotypic abnormalities. It is a rare, recessive inherited disorder with a limited number of cases reported worldwide; hence, it is important to study each case to understand its genetic complexity. An impaired activity of serine active site-containing protein 1 (SERAC1), caused by mutations, leads to defects in phosphatidylglycerol remodelling, which is important for mitochondrial function and intracellular cholesterol trafficking. In the present study, the patients (two male siblings of consanguineous Turkish parents) were analysed, whose multisystem dysfunctions, including an elevated 3-MGA concentration in early age, hearing loss and Leigh-like syndrome as determined by MRI, were consistent with MEGDEL syndrome. A novel mutation in the SERAC1 gene, in the upstream lipase domain, c.1015G>C (p.Gly339Arg) mutation located on exon 10 of the SERAC1, was identified and predicted to cause protein dysfunction. Furthermore, the results pointed towards a possible association between this mutation and the severity of MEGDEL syndrome.

Apolipoprotein E Genotypes in Patients with Prostate Cancer.

BACKGROUND: Apolipoprotein E (ApoE) is a potential inhibitor of cell proliferation, immune regulation and modulation of cell growth and differentiation; it also has a substantial role in antioxidant activity. ApoE has a potential role in prostate cancer progression. MATERIALS AND METHODS: ApoE genotyping was performed using real-time polymerase chain reaction (RT-PCR) for blood samples from a group of patients with prostate cancer (n=68) and a control group (n=78). RESULTS: The frequency of the E3/E3 genotype was significantly higher in patients compared to controls (p=0.004). E3/E3 genotype carriers were 3.6-fold more likely to be patients than controls (odds ratio=3.67, 95% confidence interval=1.451-9.155; p=0.004). Additionally, the patients with E3/E3 genotype had significantly higher Gleason score (p=0.017), and more patients with this genotype had a Gleason score higher than 7 (p=0.007). Individuals carrying the E4 allele were significantly more common in the control group (p=0.006). The frequency of the E3/E4 genotype was found to be significantly higher in controls compared to patients (p=0.007), and patients were significantly less likely to have this genotype than controls (odds ratio=0.89, 95% confidence interval=0.833-0.967, p=0.007). Individuals carrying the E2/E3 genotype had a significantly lower Gleason score (p=0.049)-all of the patients with this genotype had a Gleason score lower than 7 (p=0.024). CONCLUSION: E3/E3 genotype may be a potential risk factor for prostate cancer and high Gleason scoring. The E4 allele maybe a risk-reducing factor for prostate cancer.