Familial and sporadic GJB2-related deafness in iran: Review of gene mutations

Background: Mutations in the GJB2 gene encoding connexin 26 protein, are the main cause for autosomal recessive and sporadic non syndromic hearing loss in many populations. Here, we have taken together and reviewed results from our six previous publications, our unpublished data from ten Iranian provinces, as well as data from two previous mutation reports to provide a comprehensive collection of data for GJB2 mutations and deafness in Iran. Methods: In all, 1095 hearing impaired students and their deaf siblings from 890 families in 10 provinces of Iran were studied. The prevalence and type of the GJB2 gene mutations were investigated using nested PCR Ore screening strategy and direct sequencing of the coding exon of the gene. Results: Altogether 31 different genetic variants were detected from which 17 GJB2 mutations were identified. GJB2 mutations were found in 14.6% of deaf families (18.29% of familial and 12.7% of sporadic cases). We found GJB2 mutations in both alleles in 78% of GJB2 mutations chromosomes. However, 35deIG mutation was the most common GJB2 mutation accounting for 74.5% of the mutations in populations studied. Conclusion: Our data indicated that a specific combination of GJB2 mutations types and frequencies was presented in different populations of Iran. These results also highlight the importance of GJB2 mutations in development of hearing loss in familial and sporadic deaf families in different parts of the country and can be used as a basis of genetic counseling and clinical guideline in Iran

Nutrigenomics and nutrigenetics

The nutrients are able to interact with molecular mechanisms and modulate the physiological functions in the body. The Nutritional Genomics focuses on the interaction between bioactive food components and the genome, which includes Nutrigenetics and Nutrigenomics. The influence of nutrients on f genes expression is called Nutrigenomics, while the heterogeneous response of gene variants to nutrients, dietary components and developing nutraceticals is called Nutrigenetics. Genetic variation is known to affect food tolerances among human subpopulations and may also influence dietary requirements and raising the possibility of individualizing nutritional intake for optimal health and disease prevention on the basis of an individual's genome. Nutrigenomics provides a genetic understanding for how common dietary components affect the balance between health and disease by altering the expression and/or structure of an individual's genetic makeup. Nutrigenetics describes that the genetic profile have impact on the response of body to bioactive food components by influencing their absorption, metabolism, and site of action. In this way, considering different aspects of gene-nutrient interaction and designing appropriate diet for every specific genotype that optimize individual health, diagnosis and nutritional treatment of genome instability, we could prevent and control conversion of healthy phenotype to diseases

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Glucose-6-phosphate dehydrogenase (G6PD) Deficiency is the most prevalent enzymopathy in mankind. It has sex-linked inheritance. This enzyme exists in all cells. G6PD deficiency increases the sensitivity of red blood cells to oxidative damage. G6PD deficiency was discovered in 1950 when some people suffered hemolytic anemia as a result of taking antimalarial drugs (primaquin). Most people with G6PD deficiency do not have any symptoms, till they are exposed to certain medications, Fava beans and infections; and then their red blood cells are hemolyzed. The degree of hemolysis changes according to the degree of enzyme deficiency and the oxidant agent exposure. G6PD deficiency has many different variants and Mediterranean variant is the most common mutation in the world. G6PD deficiency is considered a health problem worldwide, especially in Asia, Middle East and Mediterranean countries. In this article, we have reviewed the importance and function of G6PD enzyme, incidence rate of G6PD deficiency in the world and Iran, genetic and variants of this enzyme, clinical manifestation, diagnosis and treatment of the enzyme deficiency

Dermatoglyphics in patients with oligo/azospermia

The study of patterns of fingerprints is important in anthropology and medical genetics, chiefly because of their diagnostic usefulness. In the present work, we studied the frequencies of various types of skin ridges of the first phalanx in patients with sever oligospermia or azospermia. In a double-blind case-control study, we determined the frequencies of fingerprints in 880 first phalanxes belonging to 48 men with sever oligospermia and 40 men with azospermia. We determined the types of fingerprints based on Galton classification. Also their FRC, TFRC and AFRC were calculated. Then the results were compared with each other and general population as control group. The most frequent type of fingerprint in both case groups was "Loop". Frequencies of different types among two groups of cases were statistically different (P<0.005). Also they were statistically different with general population (P<0.005). The largest mean of FRC in men with oligospermia was belonging to the left ring fingers (23.1) and the second to the right thumbs (21.91). The largest mean of FRC in men with azospermia was belonging to the right thumbs (23.6) and the second to the right ring fingers (22.6). The mean of TFRCs in men with oligosoermia and azospermia were 106.8 and 114.39, respectively, and the mean of AFRCs in those two groups were 14 and 11, respectively; their differences were not statistically significant. It can be concluded that qualitative feathers of the fingerprints of men with oligospermia and azospermia were different with each other and with general population. And quantitative feathers of the fingerprints in those two case groups were statistically different as well

Deafness–associated connexin 26 gene (GJB2) mutations in Iranian population

Mutations in the GJB2 gene at the DFNB1 locus on chromosome 13q12 are associated with autosomal recessive non syndromic hearing loss (ARNSHL) in many populations. A single mutation, at position 35 (35delG) accounts for approximately 30-63% of mutations in white populations with a carrier frequency of 1.5-2.5% in most European, North American and Mediterranean populations. In this study we have investigated the prevalence of the GJB2 gene mutations using direct sequencing in 43 presumed ARNSHL subjects from 34 families in an Iranian population. Eleven different genetic variants were identified. GJB2-related deafness mutations (35delG, 235delC, W24X, R184P and IVS1+1G>A) were found in 9 of 34 families (26.5%). The 35delG was the most common mutation found in 5 of 34 families (14.7%). We found one novel variant (–3517G>A) in the upstream region to the gene. The mutation frequency found in this study is lower than other ethnic groups with European ancestry, but it is indicating that mutation in GJB2 in Iranian population has contribution to ARNSHL. We have also developed a simple and accurate nested PCR assay to screen the 35delG mutation in 250 unrelated unaffected Iranian individual (controls). No 35delG heterozygous was found in the control population

Genetic Linkage Analysis of 15 DFNB Loci in a Group of Iranian Families with Autosomal Recessive Hearing Loss

Background: Hearing loss (HL) is the most frequent sensory birth defect in humans. Autosomal recessive non-syndromic HL (ARNSHL) is the most common type of hereditary HL. It is extremely heterogeneous and over 70 loci (known as DFNB) have been identified. This study was launched to determine the relative contribution of more frequent loci in a cohort of ARNSHL families. Methods: Thirty-seven Iranian families including 36 ARNSHL families and 1 family with Pendred syndrome each with >= 4 affected individuals, from seven provinces of Iran, were ascertained. DFNB1 contribution was initially studied by DNA sequencing of GJB2 and linkage analysis using the relative STR markers. The excluded families were then subjected to homozygosity mapping for fifteen ARNSHL loci. Results: Sixteen families were found to be linked to seven different known loci, including DFNB I (6 families), DFNB4 (3 families +1 family with Pendred syndrome), DFNB63 (2 families), DFNB2 (1 family), DFNB7/11 (1 family), DFNB9 (1 family) and DFNB21 (1 family). DNA sequencing of the corresponding genes is in progress to identify the pathogenic mutations. Conclusion: The genetic causes were clarified in 43.2% of the studied families, giving an overview of the causes of ARNSHL in Iran. DFNB4 is ranked second after DFNB1 in the studied cohort. More genetic and epigenetic investigations will have to be done to reveal the causes in the remaining families

Frequencies of mutations in the connexin 26 gene (GJB2) in two populations of Iran (Tehran and Tabriz)

While hearing loss has been considered to be a very heterogeneous disorder, mutations in Gap junction beta 2 (GJB2) gene encoding Connexin 26 (Cx26) protein are the major cause of autosomal recessive and sporadic non-syndromic deafness in many populations. In this study, we have investigated the prevalence of the GJB2 gene mutations using nested PCR pre screening strategy and direct sequencing method. Two hundred and seventy two hearing impaired subjects were studied from 210 families obtained from two large cities of Iran (Tehran and Tabriz). Twenty four different genetic variants were identified. Cx26 mutations were found in 53 of the 210 families (25.2) including T8M, 35delG, W24X, R32H, V371, E47X, 167delT, delE120, Y136X, R143W, R184P, 235delC and V27I+E114G. Homozygosity and compound heterozygosity for the Cx26 mutations were found in 39 of 210 (18.5) families. Homozygosity for the 35delG mutation was the most common that causes hearing loss in 28 (13.3) patients. Six novel variants H16R, E101E, K102Q, G200R, 327delG and G130A were detected in this study. As a conclusion, the present survey revealed that the rate of mutation in Cx26 gene in our area is lower than in Europe; nevertheless, this rate is regarded as a considerable cause of deafness in the cited provinces in Iran

C3 POLYMORPHISM IN HYPERLIPOPROTEINEMIA (HLP)

C3 typing was performed, by agarose gel electrophorisis, in 147 German patients suffering from hyperlipoproteinemia. The control group consisted of 322 healthy Germans. High frequencies of non-typeable sera, varying between 16.66 and 35.71% in different HLP types, found in the present investigation are notable and are a clue for chemical denaturation of C3 protein in HLP patients. Statistical analysis showed significant results (P.0.001) in all five HLP types, as well as in the total, in comparison with the control group

HIGH LEVEL OF GST-P mRNA IN ISLAND TYPE OF RAT ASCITES HEPATOMA CELL LINES

Several cell lines (18) of poorly differentiated rat ascites hepatomas which grown intraperitoneally were analyzed with respect to their mRNA levels of GST-P and albumin. The expression of albumin was dramatically decreased and became undetectable in all of the examined hepatomas compared with normal rat liver. The GST-P mRNA level in the hepatomas was correlated with their ability for formation of cellular islands in ascites. The island types, expressed GST-P at high level and the free type ones showed very low level of GST-P mRNA

Nutrigenomics and nutrigenetics

The nutrients are able to interact with molecular mechanisms and modulate the physiological functions in the body. The Nutritional Genomics focuses on the interaction between bioactive food components and the genome, which includes Nutrigenetics and Nutrigenomics. The influence of nutrients on f genes expression is called Nutrigenomics, while the heterogeneous response of gene variants to nutrients, dietary components and developing nutraceticals is called Nutrigenetics. Genetic variation is known to affect food tolerances among human subpopulations and may also influence dietary requirements and raising the possibility of individualizing nutritional intake for optimal health and disease prevention on the basis of an individual�s genome. Nutrigenomics provides a genetic understanding for how common dietary components affect the balance between health and disease by altering the expression and/or structure of an individual's genetic makeup. Nutrigenetics describes that the genetic profile have impact on the response of body to bioactive food components by influencing their absorption, metabolism, and site of action. In this way, considering different aspects of gene�nutrient interaction and designing appropriate diet for every specific genotype that optimize individual health, diagnosis and nutritional treatment of genome instability, we could prevent and control conversion of healthy phenotype to diseases. © 2010, Iranian Journal of Public Health. All rights reserved