Mitochondrial genetic variation in Iranian infertile men with varicocele

Background: Several recent studies have shown that mitochondrial DNA mutations lead to major disabilities and premature death in carriers. More than 150 mutations in human mitochondrial DNA [mtDNA] genes have been associated with a wide spectrum of disorders. Varicocele, one of the causes of infertility in men wherein abnormal inflexion and distension of veins of the pampiniform plexus is observed within spermatic cord, can increase reactive oxygen species [ROS] production in semen and cause oxidative stress and sperm dysfunction in patients. Given that mitochondria are the source of ROS production in cells, the aim of this study was to scan nine mitochondrial genes [MT-COX2, MT-tRNA[Lys], MT-ATP8, MT-ATP6, MT-COX3, MT-tRNA[Gly], MT-ND3, MT-tRNA[Arg]and MT-ND4L] for mutations in infertile patients with varicocele

Materials and Methods: In this cross-sectional study, polymerase chain reaction-single strand conformation polymorphism [PCR-SSCP] and DNA sequencing were used to detect and identify point mutations respectively in 9 mitochondrial genes in 72 infertile men with varicocele and 159 fertile men. In brief, the samples showing altered electrophoretic patterns of DNA in the SSCP gel were sent for DNA sequencing to identify the exact nucleotide variation

Results: Ten type nucleotide variants were detected exclusively in mitochondrial DNA of infertile men. These include six novel nucleotide changes and four variants previously reported for other disorders

Conclusion: Mutations in mitochondrial genes may affect respiratory complexes in combination with environmental risk factors. Therefore these nucleotide variants probably lead to impaired ATP synthesis and mitochondrial function ultimately interfering with sperm motility and infertility

Mutation analysis of TNP1 gene in infertile men with varicocele

Varicocele is associated with the failure of ipsilateral testicular growth and development, and the symptoms of pain and reduced fertility. The highly condensed structure of the sperm nuclear chromatin is provided by proper expression of Transition Nuclear Protein [TNP] genes, so any dysregulational expression of these genes results in abnormal spermatogenesis and infertility. The aim of present study was to assess the association between TNP1 mutations and varicocele in Iranian infertile men. Analysis of association between TNP1 gene mutation and varicocele phenotype was performed using PCR and Single-Stranded Conformational Polymorphism technique and DNA sequencing in 82 varicocele infertile men and 80 control subjects. Sequence analysis was identified one variant in this gene that found in 15 infertile men and was absent in control group. This variant was a single nucleotide polymorphism that were identified in the intron region of this gene at position g.IVS1+75T>C. The effect of this nucleotide substitution in intronic region of the TNP1 gene and their role on expression remains to be determined

Increased Prevalence 12308 A > G mutation in Mitochondrial tRNA[Leu [CUN]] Gene Associated with earlier Age of Onset in Friedreich Ataxia

Friedreich ataxia [FRDA] is an inherited recessive disorder. Mitochondrial DNA is a candidate modifying factor for FRDA.The purpose of this study was to investigate the relationship between the tRNA[Leu [CUN]] 12308 A> G mutation and age of onset in Friedreich ataxia. The 12308 A> G substitution in mitochondrial tRNA[Leu [CUN]] was examined in DNA samples from 30 Friedreich ataxia patients and 48 control subjects by temporal temperature gradient gel electrophoresis [TTGE] and sequencing. Logistic regression was used to determine of cutoff age of onset. Twenty-two patients had the 12308 A> G mutation, and we found that its overall prevalence was significantly higher in 20 patients aged 17 years or younger than in 2 patients aged over 17 years [90% versus 10%]. The 12308 A> G mutation lies in a region that has been highly conserved between species. Our results show that the 12308 A > G mutation is associated with earlier age of onset in Friedreich ataxia. Thus, this mutation might cause the younger age of onset in FRDA

Novel missense mitochondrial ND4L gene mutations in friedreich's ataxia

The mitochondrial defects in Friedreich's ataxia have been reported in many researches. Mitochondrial DNA is one of the candidates for defects in mitochondrion, and complex I is the first and one of the largest catalytic complexes of oxidative phosphorylation [OXPHOS] system. We searched the mitochondrial ND4L gene for mutations by TTGE and sequencing on 30 FRDA patients and 35 healthy controls. We found 3 missense mutations [m.l0506A>G [T13A], m.1053QG>A [V21M], and m.10653G>A [A62T]] in four patients whose m.10530G>A and m.10653G>A were not reported previously. In two patients, heteroplasmic m.10530G>A mutation was detected. They showed a very early ataxia syndrome. Our results showed that the number of mutations in FRDA patients was higher than that in the control cases [P= 0.0287]. Although this disease is due to nuclear gene mutation, the presence of these mutations might be responsible for further mitochondrial defects and the increase of the gravity of the disease. Thus, it should be considered in patients with this disorder