The influence of Nrf2 gene promoter methylation on gene expression and oxidative stress parameters in preeclampsia.

BACKGROUND AND AIMS: Preeclampsia (PE) is a serious medical condition that usually causes high blood pressure and affects multiple organs. Considering the adverse effect of oxidative stress on the process of PE in pregnant women and regarding the role of the Nrf2 gene in placental oxidative pathways, this study was conducted to investigate the DNA methylation status of Nrf2 in PE and healthy pregnant women. MATERIALS AND METHODS: The present case-control study consisted of 70 PE and 70 healthy pregnant women. Blood and placenta samples were taken from all subjects, and the percentage of the Nrf2 gene methylation in the samples was assessed by the Methyl Light PCR method. Also, the Nrf2 gene expression was evaluated by real-time PCR. The total antioxidant capacity (TAC) and total oxidative status (TOS) were measured by the colorimetric method. RESULTS: In PE women, there was a significant increase in blood pressure, term of pregnancy, and BMI. In addition, there were enhanced Nrf2 DNA methylation percentage in placenta tissue and increased TOS levels in placenta tissue and blood compared to healthy pregnant women (P < 0.05). Also, in the PE group, there was a significant decrease in Nrf2 gene expression and TAC level in placenta tissue compared to the control group (P < 0.05). CONCLUSION: The Nrf2 gene undergoes epigenetic modifications of DNA hypermethylation in the PE placenta. Decreased expression of this gene and the changes in the level of oxidative parameters (TAC, TOS) confirm it.

Reporting a novel growth hormone receptor gene variant in an Iranian consanguineous pedigree with Laron syndrome: a case report.

BACKGROUND: Human growth hormone (hGH) plays a crucial role in growth by binding to growth hormone receptor (GHR) in target cells. Binding of GH molecules to their cognate receptors triggers downstream signaling pathways leading to the transcription of several genes, including insulin-like growth factor (IGF)-1. Pathogenic variants in the GHR gene can result in structural and functional defects in the GHR protein, leading to Laron Syndrome (LS) with the primary clinical manifestation of short stature. So far, around 100 GHR variants have been reported, mostly biallelic, as causing LS. CASE PRESENTATION: We report on three siblings from an Iranian consanguineous family who presented with dwarfism. Whole-exome sequencing (WES) was performed on the proband, revealing a novel homozygous missense variant in the GHR gene (NM_000163.5; c.610 T > A, p.(Trp204Arg)) classified as a likely pathogenic variant according to the recommendation of the American College of Medical Genetics (ACMG). Co-segregation analysis was investigated using Sanger sequencing. CONCLUSIONS: To date, approximately 400-500 LS cases with GHR biallelic variants, out of them 10 patients originating from Iran, have been described in the literature. Given the high rate of consanguineous marriages in the Iranian population, the frequency of LS is expected to be higher, which might be explained by undiagnosed cases. Early diagnosis of LS is very important, as treatment is available for this condition.

The Potential of miR-21 in Stem Cell Differentiation and its Application in Tissue Engineering and Regenerative Medicine.

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two important types of non-coding RNAs that are not translated into protein. These molecules can regulate various biological processes, including stem cell differentiation and self-renewal. One of the first known miRNAs in mammals is miR-21. Cancer-related studies have shown that this miRNA has proto-oncogene activity and is elevated in cancers. However, it is confirmed that miR-21 inhibits stem cell pluripotency and self-renewal and induces differentiation by targeting various genes. Regenerative medicine is a field of medical science that tries to regenerate and repair damaged tissues. Various studies have shown that miR-21 plays an essential role in regenerative medicine by affecting stem cell proliferation and differentiation. In this review, we will discuss the function of miR-21 in regenerative medicine of the liver, nerve, spinal cord, wound, bone, and dental tissues. In addition, the function of natural compounds and lncRNAs will be analyzed as potential regulators of miR-21 expression in regenerative medicine.

The pathogenicity classification of PAH gene variants in the Iranian population.

Till now not many studies have been conducted to classify PAH gene variants according to American College of Medical Genetics and Genomics (ACMG-AMP) guidelines. The aim of this study was to collect all PAH gene variants reported among Iranian population and investigate their pathogenicity based on ACMG-AMP guidelines. Systematic collection of PAH gene variants, verification of variants, in silico analysis, and application of ACMG-AMP guidelines were the main steps in performing the present study. A total of 267 unique variants were identified; according to ACMG-AMP guidelines, 90, 40, 71, 14, and 52 variants were classified as pathogenic (P), likely pathogenic (LP), variant of uncertain significance (VUS), likely benign (LB), and benign (B), respectively. The need to pay more attention to synonymous and missense variants with low or no impact on protein function as well as intronic variants, whether they are deep or are close to intron/exon boundaries, was a highlight of this study. Due to the fact that few functional studies are performed on these variants, it is suggested that they be analyzed first using bioinformatics tools, and if positive results are obtained, then functional studies can be designed.

α-Thalassemia Mutations in Ilam Province, West Iran.

Despite several studies performed in different provinces of Iran to identify the spectrum of α-globin gene mutations, no such study has so far been carried out in Ilam Province. A total of 274 individuals, including 201 α-thalassemia (α-thal) carriers and 73 normal subjects, originating from the northern counties of Ilam Province, participated in this study. Analysis of α-globin defects was performed using multiplex gap-polymerase chain reaction (gap-PCR), amplification refractory mutation system (ARMS)-PCR and direct sequencing, which revealed a total of 11 different mutations and 22 different genotypes. The -α3.7 (rightward) (NG_000006.1: g.34164_37967del3804), α-5 ntα (HBA2: c.95 + 2_95 + 6delTGAGG), and -α4.2 (leftward) deletions were the most prevalent mutations identified in our study, with frequencies of 66.23, 10.09 and 8.33%, respectively. In conclusion, the present study showed that the α-thal mutation spectrum in Ilam Province, at least in the northern part of the province, is different from that in other geographical regions of Iran. These results increase our knowledge about the spectrum and distribution of α-globin gene mutations in Iran.

CFTR gene mutation spectrum among 735 Iranian patients with cystic fibrosis: A comprehensive systematic review.

In this study, the spectrum and frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations previously reported among Iranian cystic fibrosis (CF) patients have been reviewed and discussed. Using the keywords of Cystic Fibrosis, CF, CFTR, and Iran, along with their Persian equivalents, a comprehensive search was performed on the online databases. After applying the inclusion and exclusion criteria, 16 articles with an overall sample of 735 Iranian patients with CF, were included in this systematic review. A total of 101 different CFTR gene variants had been reported. The mutation of p.Phe508del (c.1521_1523delCTT) (21.22%) was the most frequent one among Iranian patients with CF. In conclusion, due to the fact that in many provinces of Iran no specific study has been done so far, it seems that the CFTR gene mutation spectrum in patients with CF from Iran is much wider.

Spectrum of PAH gene mutations in 1547 phenylketonuria patients from Iran: a comprehensive systematic review.

As one of the highest prevalence rates in the world, the prevalence of Phenylketonuria (PKU) in Iran has been estimated at 16.5 per 100,000 neonates. The objective of this study was to evaluate the spectrum and frequency of mutations of the phenylalanine hydroxylase (PAH) gene in Iranian PKU patients. A systematic review was carried out on previous studies on PAH gene mutations in Iranian PKU patients. A complete search was carried out on the on-line databases of Scopus, Web of Science, PubMed/Medline, ProQuest, Science Direct, Magiran, SID and the search engine Google Scholar. The keywords of Phenylketonuria, PKU, Phenylalanine Hydroxylase, PAH, and Iran, as well as their Persian equivalents, in all possible combinations were used. Finally, a total of 21 eligible articles with a sample size of 1547 Iranian PKU patients, published between 2003 and 2020, were included in our systematic review. A total of 129 different PAH gene mutations including, IVS10-11G > A (c.1066-11G > A) (19.23%), p.R261Q (c.782G > A) (7.63%), p.P281L (c.842C > T) (6.24%), IVS2 + 5G > C (c.168 + 5G > C) (5.75%), p.R243* (c.727C > T) (3.59%), IVS9 + 5G > A (c.969 + 5G > A) (2.84%), p.R176* (c.526C > T) (2.42%), p.Lys363Nfs*37 (c.1089delG) (2.13%), IVS11 + 1G > C (c.1199 + 1G > C) (2.07%) and p.L48S (c.143 T > C) (2.04%) were identified. The spectrum and frequency of mutations observed in Iran were closer to those observed in the Mediterranean countries. Our results are valuable in planning panel-based studies in provinces with incomplete data on PAH gene mutations. This study is a good reference for genetic counselors and physicians who advise couples in making decisions to maintain or terminate a pregnancy.

Cytogenetic Analysis of 570 Couples with Recurrent Pregnancy Loss: Reporting 11 Years of Experience.

OBJECTIVES: Recurrent pregnancy loss (RPL) is a serious complication of pregnancies, affecting almost 2%-5% of couples. Among numerous underlying causes, chromosomal anomalies in one of the partners are regarded as important issues, with varying frequencies among different populations. In this study, we aimed to determine the prevalence of chromosomal abnormalities and chromosome polymorphisms in couples with a history of RPL from Kermanshah province, west of Iran. MATERIALS AND METHODS: In this 11-year retrospective study, a total of 1140 cases with two or more spontaneous abortions were recruited and studied according to standard cytogenetic analysis. RESULTS: From a total of 1140 reviewed blood samples, 1011 people (88.5%) had a normal karyotype and 129 people (11.5%) had chromosomal aberrations. These aberrations were found in 62 females and 67 males. The prevalence of chromosomal abnormalities was as follows: 18 (1.5%) structural aberrations, 1 numerical anomaly and 110 (9.6%) apparently normal polymorphic variants. CONCLUSIONS: Our findings could determine the underlying cause of RPL in 1.5% of the population while the majority still remained unexplained. This emphasizes the importance of searching for other genetic and nongenetic causes of RPL in apparently idiopathic cases of RPL.

Distribution of HBB Gene Mutations in the Kurdish Population of Ilam Province, West Iran.

ß-Thalassemia (ß-thal) is one of the most common diseases in Iran. Here, we report the spectrum of HBB gene mutations in 176 Kurdish ß-thal carriers from the northern part of Ilam Province, Iran. The amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique was used to identify common ß-globin gene mutations observed in Iran. Samples negative on ARMS-PCR were analyzed by direct sequencing of the ß-globin gene. In total, 12 different mutations were identified on the ß-globin gene. The mutations of IVS-II-1 (G>A) (HBB: c.315+1G>A), codons 8/9 (+G) (HBB: c.27_28insG), codons 36/37 (-T) (HBB: c.112delT) and IVS-I-110 (G>A) (HBB: c.93-21G>A), were the most prevalent mutations in our samples, with frequencies of 59.09, 10.80, 7.95 and 7.39%, respectively. In general, the mutation spectrum of the ß-globin gene in the northern part of Ilam Province is most similar to that in other western provinces of Iran. On the other hand, due to the high prevalence of carriers and ß-thal major (ß-TM) patients in this province, our results can be helpful in identifying carriers as well as at-risk fetuses through the prenatal diagnosis program.

Molecular Genetic Analysis of α-Thalassemia in Hamadan Province, West Iran.

Identifying couples who are carriers of thalassemia-causing mutations, followed by prenatal diagnosis (PND), is undoubtedly an effective way to prevent the birth of children with the disease. Our aim in this study was to report for the first time the spectrum of α-globin gene mutations in the population living in Hamadan Province, West Iran. Multiplex gap-polymerase chain reaction (gap-PCR), amplification refractory mutation system (ARMS)-PCR, and direct DNA sequencing of HBA1 and HBA2 genes were used to identify the α-thalassemia (α-thal)-causing mutations in a cohort of 389 individuals including 328 α-thal carriers and 61 normal subjects. A total of 17 different mutations and 25 different genotypes were detected. The -α3.7 (rightward) deletion (NG_000006.1: g.34164_37967del3804) was the most frequent mutation, accounting for more than half of all mutations (61.04%). This study revealed that there is a variety of α-thal mutations and α-thal genotypes in Hamadan Province, West Iran. This observation is probably due to the complexity of the Hamadan Province population that is composed of Persians (Fars), Turks, Kurds, and Lurs/Laks. In conclusion, our results demonstrated the spectrum of mutations in α-globin genes in Iran and increased our understanding of their distribution in this country.

Haplotype analysis of the CFTR gene on normal and mutant CFTR genes.

BACKGROUND: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are responsible for Cystic Fibrosis (CF) disease. Since the distribution of polymorphisms varies among populations, a comparison between the frequency of CFTR polymorphisms in patients and healthy population may further identify their role in CF disease. The results obtained from this research may facilitate the prediction of disease phenotype in prenatal diagnosis or newborn screening program as well as determine the possible associations between haplotypes and specific mutations. METHODS: Blood samples collected from 27 unrelated West Iranian families contain at least one CF patient and 55 control families with no history of CF. Samples were analyzed for c.1210-12 T [5-9], c.1242-35-1242-12GT [8-10], c.744-33GATT [6-8] and c.869 + 11C > T polymorphisms by automated direct DNA sequencing following DNA extraction. RESULTS: Our results showed that the T7 allele is the most common allele in normal and non-ΔF508 CF chromosomes with the frequencies of 93.6% and 100%, respectively. Conversely, T9 was the only allele detected in ΔF508 chromosomes. Moreover, the c.1242-35-1242-12GT analysis showed that (TG)11 repeat was the most common dinucleotide repeat in both, non-ΔF508 and normal chromosomes with the frequencies of 91% and 71%, respectively. The c.744-33GATT and c.869 + 11C > T polymorphism analyses indicated that (GATT)6 and T allele are only found in ΔF508 CF chromosomes. Besides, the [T7-TG11-GATT7-C] haplotype was the most common haplotype in both, normal and non-ΔF508 CF subjects while the [T9-TG10- GATT6-T] haplotype was only detected in CF patients carrying ΔF508 mutation. CONCLUSIONS: Our findings identified an informative haplotype that could be used in genetic counseling, prenatal diagnosis and future screening of CF in Iran.

Severe α-Thalassemia Due to Compound Heterozygosity for Hb Adana (α59 Gly>Asp) (HBA1: c.179G > A) and Codon 127 (A > T) (HBA2: c.382A > T) in an Iranian Family.

We describe a novel compound heterozygous genotype which consists of two point mutations named Hb Adana (HBA1: c.179G>A) and codon 127 (HBA2: c.382A>T) in a Kurdish family with two girls affected with severe α-thalassemia (α-thal). Both patients (the proband and her sister) had a history of splenectomy during childhood. Although the proband had no blood transfusion history, her affected sister has had two blood transfusions so far. In conclusion, diagnosing and reporting new genotypes on the α-globin genes will improve our knowledge about complicated genotype-phenotype correlations in α-thal disorder.

The Spectrum of α-Thalassemia Mutations in Kurdistan Province, West Iran.

In order to identify the α-thalassemia (α-thal) mutation spectrum in Kurdistan Province, West Iran, a total of 217 individuals, including 154 α-thal carriers and 63 normal subjects were investigated in this study. Molecular analysis of α1- and α2-globin genes using multiplex gap-polymerase chain reaction (gap-PCR), amplification refractory mutation system (ARMS)-PCR or direct DNA sequencing, showed 11 different α-globin variants. The -α3.7 (rightward) deletion (NG_000006.1: g.34164_37967del3804) (70.32%), polyadenylation signal (polyA2) site (AATAAA>AATGAA) (αpolyA2α) (HBA2: c.*92A>G) (7.74%), -α4.2 (leftward) deletion (6.45%) and codon 59 (or Hb Adana) (G>A) (ααcodon 59) (HBA1: c.179G>A) (4.52%) were the most frequent mutations in the present study. In conclusion, the spectrum of α-thal mutations in Kurdistan Province is closest to that in western provinces of Iran (Kurdish and Laki populations). In addition, it was revealed that the codon 59 mutation is common in the Kurdish population. On the other hand, despite the same ethnic background of Kurds in Iran and Iraq, the - -MED I double gene deletion and polyA2 point mutation have different distributions in these two populations. Therefore, further studies are needed to identify the cause of these differences.

The status of PAH gene-VNTR alleles and mini-haplotypes associations with PAH gene mutations in Iranian Kurdish PKU patients.

Background: The analysis of haplotypes/mini-haplotypes in the PAH gene has been used as an informative tool in several genetic anthropology studies. Considering the notion that Iranian population is one of the most heterogeneous i the world, this study was conducted to evaluate the association of VNTR-STR mini-haplotypes with the PAH gene mutations in PKU patients in Kermanshah province. Methods: A total of 24 unrelated Kurdish PKU patients with the known PAH gene causing mutations and 72 healthy controls were selected. The DNA fragments containing VNTR and STR systems were amplified by polymerase chain reaction (PCR). For VNTR system, PCR products were separated using electrophoresis on 2.5% agarose gel. For STR system, the samples were analyzed using DNA sequencing analysis version 5.2 software. Results: Overall, 5 PAH-VNTR-alleles, including VNTR3, 7, 8, 9, 12, and 3 PAH-STR-alleles, including STR238, 242, and 250, were detected in this study. VNTR3 and 8 alleles had the most frequency among healthy controls. Also, 6 different mini-haplotype alleles were found to be associated with PKU chromosomes. The 2 most prevalent mutations in Kermanshah province, IVS2+5G>C and IVS9+5G>A, were strongly linked to mini-haplotypes 9/242 and 8/238, respectively. Conclusion: The distributions and frequencies of VNTR alleles in Kurdish population have the most similarity to alleles previously described in European Caucasian families. Moreover, since the most common mutations in Kermanshah PKU chromosomes are rare and this was the first study on mini-haplotypes VNTR/STR among Iranian Kurdish PKU patients, given that this study was the first of its kind, it was not possible to compare its results with that of other studies on Iranian and non-Iranian populations.

The Spectrum of α-Thalassemia Mutations in the Lak Population of Iran.

α-Thalassemia (α-thal) is one of the most common genetic disorders worldwide. The aim of this study was to investigate for the first time the α-thal mutation spectrum in the Lak population living in Lorestan Province, Iran. One hundred and seventy-six α-thal carriers participated in the study. Multiplex gap-polymerase chain reaction (gap-PCR), amplification refractory mutation system (ARMS)-PCR and direct sequencing were used for the detection of different mutations on the α-globin (HBA1 and HBA2) genes. A total of 11 different mutations was identified. The -α3.7 (rightward; NG_000006.1: g.34164_37967del3804) deletion was observed most frequently (56.35%), followed by α-5 ntα (HBA2: c.95+2_95+6delTGAGG), αpolyA2α (HBA2: c.*92A>G) and - -MED I (NG_000006.1: g.24664_41064del16401), with frequencies of 15.47, 9.39, and 6.08%, respectively. These four mutations accounted for more than 87.0% of the total mutated alleles. Moreover, 19 different genotypes were identified. The types and distribution pattern of the mutations identified in this study, in comparison with other studies conducted in Iran, was most similar to the Kurdish population of Kermanshah Province, Iran. Due to the lack of information on α-thal in Lorestan Province, it was not possible to compare the mutation spectrum in the Lur and Lak populations. In conclusion, our results may help in setting up a strategy for an α-thal screening program and genetic counseling in the Lak people.

Characterization of the IVS-II-821 (A>C) (HBB: c.316-30A>C) Mutation in a ß-Thalassemia Phenotype in Iran.

ß-Thalassemia (ß-thal) is the most frequently observed hereditary blood disorder that results from genetic defects causing deficient synthesis of hemoglobin (Hb) polypeptide chains. Detecting thalassemia mutations are necessary for prenatal diagnosis (PND) programs leading a better quality of life for the patients, as well as a reduction in the cost of their medical care. There are more than 900 different genomic mutations of the ß-globin gene described in the human hemoglobin variant (HbVar) database. In this study, we identified a mid-intronic mutation at IVS-II-821 (A>C) (HBB: c.316-30A>C) position in the HBB gene of an Iranian proband and two of her siblings that was associated with ß-thal clinical features. Direct DNA sequence analysis was performed by mutation scanning of the ß-globin gene. Based on the observed ß-thal phenotype and bioinformatics analysis results, we concluded that this ß-globin gene mutation was associated with a mild phenotype of ß-thal through activating potential splice sites by creating exonic splicing enhancers (ESEs), exon-identity element (EIE) and exonic splicing regulatory sequences (ESRs) sites.

The Spectrum of ß-Thalassemia Mutations in Hamadan Province, West Iran.

ß-Thalassemia (ß-thal) is one of the most common hemoglobinopathies worldwide and is caused by mutations on the ß-globin (HBB) gene. The aim of the present study was to determine the mutation spectrum of the ß-globin gene in ß-thal carriers who were originally from Hamadan Province, Western Iran. Two hundred and eighty-two ß-thal carriers participated in the study. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and direct sequencing were used for detection of different mutations. A total of 25 different mutations, including 21 ß-thal mutations and four other hemoglobin (Hb) variants, in 280 ß-thal carriers (99.3%) were detected in the present study. Three types of mutations including IVS-II-1 (G>A) (HBB: c.315+1G>A) (26.24%), codons 8/9 (+G) (HBB: c.27_28insG) (14.54%) and codons 36/37 (-T) (HBB: c.112delT) (12.76%) accounted for more than 50.0% of the identified mutations. Moreover, IVS-I-110 (G>A) (HBB: c.93-21G>A), codon 44 (-C) (HBB: c.135delC) and IVS-I (25 bp deletion) (HBB: c.93-21_del), had frequencies of 7.09, 7.09 and 5.67%, respectively. Allele frequencies of the remaining 19 mutations were less than 5.0%. This study is the first comprehensive study on a large sample size in Hamadan Province, Iran. In conclusion, the present study significantly increased the spectrum of HBB gene mutations in Hamadan Province compared with previous studies. Therefore, these results can be helpful in identifying ß-thal carriers and at-risk fetuses through prenatal diagnosis (PND).

Association between activity and genotypes of paraoxonase1 L55M (rs854560) increases the disease activity of rheumatoid arthritis through oxidative stress.

Rheumatoid arthritis (RA) is considered as a long-term autoimmune disorder. Gene polymorphism and oxidative stress might be involved in the pathogenesis of the disease. We aimed to determine the association between PON-1L55M polymorphism and its effects on inflammatory markers such as anti-cytroline circulated-peptide (CCP)-antibodies, C-reactive protein (CRP), neopterin serum concentration, arylesterase (ARE) and butyrylcholinesterase (BuChE) activities and total-antioxidant-capacity (TAC) level with the activity of disease in RA patients. This case-control study consisted of 419 RA patients and 397 gender-age-matched unrelated healthy controls from the west of Iran. PON1-L55M polymorphism was detected by real-time-PCR. The TAC level, serum BuChE and ARE activities were determined spectrophotometrically. Anti-CCP-antibody and CRP were measured by ELISA and neopterin level was detected by HPLC. The PON1-M55 allele was associated with increased risk of the RA in cases with moderate or high activity (OR = 1.43, p = 0.023) and also in cases with the presence of anti-CCP antibody (OR = 1.51, p = 0.009). Synergistic effects of PON1 M55 and Q192 alleles resulted in 2.14 times (p = 0.021) increased disease activity among RA patients with moderate or high activity of the disease. RA patients carried both M (PON1 L55M) and Q alleles (PON1Q192R) had higher concentrations of neopterin (p = 0.003), anti-CCP-antibody (p < 0.001) and CRP (p = 0.026) and significantly lower TAC level (p < 0.001) and ARE (p < 0.001) activity compared to controls. The current study suggests there might be a relationship between genetic and activity of PON. Also, the PON1L55M and PON1Q192R could act in synergy to increase the risk of RA and enhance the level of oxidative stress markers.

Spectrum of Phenylalanine Hydroxylase Gene Mutations in Hamadan and Lorestan Provinces of Iran and Their Associations with Variable Number of Tandem Repeat Alleles.

Phenylketonuria (PKU) is one of the most common known inherited metabolic diseases. The present study aimed to investigate the status of molecular defects in phenylalanine hydroxylase (PAH) gene in western Iranian PKU patients (predominantly from Kermanshah, Hamadan, and Lorestan provinces) during 2014-2016. Additionally, the results were compared with similar studies in Iran. Nucleotide sequence analysis of all 13 exons and their flanking intronic regions of the PAH gene was performed in 18 western Iranian PKU patients. Moreover, a variable number of tandem repeat (VNTR) located in the PAH gene was studied. The results revealed a mutational spectrum encompassing 11 distinct mutations distributed along the PAH gene sequence on 34 of the 36 mutant alleles (diagnostic efficiency of 94.4%). Also, four PAH VNTR alleles (with repeats of 3, 7, 8 and 9) were detected. The three most frequent mutations were IVS9+5G>A, IVS7-5T>C, and p.P281L with the frequency of 27.8%, 11%, and 11%, respectively. The results showed that there is not only a consanguineous relation, but also a difference in PAH characters of mutations between Kermanshah and the other two parts of western Iran (Hamadan and Lorestan). Also, it seems that the spectrum of mutations in western Iran is relatively distinct from other parts of the country, suggesting that this region might be a special PAH gene distribution region. Moreover, our findings can be useful in the identification of genotype to phenotype relationship in patients, and provide future abilities for confirmatory diagnostic testing, prognosis, and predict the severity of PKU patients.

CFTR Mutation Analysis in Western Iran: Identification of Two Novel Mutations.

BACKGROUND: Cystic fibrosis (CF) is one of the most common autosomal recessive disorders in Caucasian population. The incidence of disorder varies among different religious, ethnic and geographical isolates. The aim of this study was to identify the spectrum and the frequency of known and unknown disease-causing mutations in Iranian CF patients. METHODS: Genomic DNA was extracted from peripheral whole blood with a QIAamp DNA Mini-Kit. Mutation analysis was done in the CFTR gene including complete coding region and intron/exon boundaries using a direct sequencing method. RESULTS: In general, ten mutations were identified in 27 CF cases. Two out of 10 mutations, 754delT and GGTGGCdel/TTGins, were reported as novel mutations. The most common observed mutations in patients were R334W (40.74%), ΔF508 (18.5%), K710X (12.96%) and D110H (5.5%), 1897C>G (1.85%), R1162X (1.85%), S466X (1.85%) and T1036I (1.85%). CONCLUSION: The finding indicated a unique mutation panel which can be used in genetic counseling, prenatal diagnosis and future screening of CF in Iran. Although ΔF508 is the most common mutation in other populations including Caucasian, this mutation seem not to have an important role in Iranian CF patients. Findings suggest that a different approach in molecular genetics diagnostic strategies in Middle Eastern countries including Iran should be considered.