[Frequency of the common mitochondrial DNA [mtDNA] mutations in non-syndromic hearing impairment in southwest subpopulations of Iran]

Although, most hereditary non-syndromic hearing impairment [NSHI] is due to mutation in nuclear genes, role of mtDNA mutations in causing deafness becoming much more clear in recent years. The aim of the present study was to screen the A1555G, C1494T, A3243G and A7445G mutations in non-syndromic hearing impairment patients in two provinces of southwest of Iran. In this descriptive laboratory study, 150 subjects with acquired and prelingual autosomal recessive NSHI from Chaharmahal va Bakhtiari province and 46 unrelated probands with postlingual NSHI from Bushehr province [negative for GJB2 mutations] were screened for the presence of the common mtDNA mutations using PCR-RFLP method that followed by direct sequencing for confirming the observed mtDNA mutations. None of these mutations was found in subjects with acquired and prelingual autosomal recessive NSHI from Chaharmahal va Bakhtiari province, but mutation A1555G with frequency of 4.35% was found in postlingual NSHI patients in Bushehr province. This investigation shows that apparently, mtDNA mutations play a more significant role role in the etiology of postlingual NSHI in comparison with prelingual NSHI

[Report of a novel mutation in RB1 gene from an Iranian retinoblastoma patient and its effect on splicing pattern of mRNA]

Mutations in RB1 gene may lead to retinoblastoma which is the most common solid intraocular tumor in under-six year old children. To date, a wide spectrum of the mutations has been reported in the splicing of RB1 which either affect splicing sequences or splicing regulatory elements. This report introduces a new mutation in RB1and its influence on the splicing of mRNA. Case report: In the present survey, mutation analysis was done in an Iranian patient with sporadic unilateral retinoblastoma using direct sequencing and MLPA. Also, RB1 gene splicing pattern was analyzed by RT-PCR method. As a result, a same-sense nucleotide change [g.70 320C>T] was found near the 5' end of exon 12. This alteration disrupts the consensus sequence of an exonic splicing enhancer and changes the binding site of SC-35 protein. Structural analysis of cDNA in this patient showed the disruption of normal splicing pattern and the skipping of exon 12 from the RB1 transcript. Based on these findings, it may be reasonable to conclude that the above nucleotide change could be a pathogenic mutation. Also, for the first time we report an evidence for the presence of an exonic splicing enhancer in the exon 12 of the RB1 gene

[Molecular investigation of mtDNA A1555G, A3243G and A7445G mutations among the non syndromic hearing loss cases in Fars, Iran]

Hearing loss is a sensorineural disorder occuring in 1 out of 500 births. It happens due to some genetic/environmental causes or both. More than 60% of cases are noninherited and 80% non syndromic with autosomal recessive inheritance. In the present study we investigated the frequency of mtDNA A1555G, A3243 and A7445G mutations among the patients in Fars province. Seventy two non syndromic hearing loss subjects were studied. DNA was extracted using standard phenol-chloroform method. The screening of the mitochondrial gene mutations were performed using PCR-RFLP procedure. Finally, the possible mutations were confirmed by direct sequencing. None of the A1555G, A3243G and A7445G mutations was detected in this study. However, destroying a MTTL1 restriction site for the investigation of A3243G mutation, revealed a G3316A with allelic variant of 1.4% in the deaf subjects. Our data indicated that the mitochondrial A1555G, A3243 and A7445G mutations have no role in auditory deficits in patients studied

Correlation of del13q, del11q and trisomy 12 with laboratory and clinical features of chronic lymphocytic leukemia in Iranian patients

There is a strong association between chromosomal abnormalities and laboratory features and clinical course of the B-cell chronic lymphocytic leukemia [B-CLL]. The aim of this study was to investigate the frequency and correlation of cytogenetic aberrations with laboratory and clinical features of the disease. Clinical and laboratory features of 65 CLL patients were collected from their hospital profiles and their blood and/or bone marrow were examined by conventional cytogenetics and interphase FISH methods. Conventional cytogenetic methods identified 27.7% chromosomal abnormalities in 65 patients. I-FISH analysis for del13q, del11q and trisomy 12 revealed abnormality in 75.4% of patients. The results showed that IFISH improved the detection rate of chromosomal abnormalities and it enhanced detection. Statistical analysis was performed on sex, age, family history, Rai stage and CD markers on trisomy 12, del 11q and del 13q subgroups. There was a high frequency of Ray stages I and II within del13q subgroup, Rai stages III and IV within del11q subgroup and Rai stage II within trisomy 12 subgroup. Mean of CD38 in patients with del 11q was significantly higher than mean of patients with trisomy 12 and del 13q. High level of CD38 and presence of del11q indicated a poor prognosis and low level of CD38 and presence of del13q was indicative of good prognosis in Iranian B-CLL patients. Trisomy 12 had an intermediate prognostic value