Report of an Iranian child with chronicabdominal pain and constipation diagnosedas glycogen storage disease type IX: a casereport
Abstract :
Background Glycogen storage disease type IX is a rare disorder that can cause a wide variety of symptoms depending on the specific deficiency of the phosphorylase kinase enzyme and the organs it affects.
Case presentation A 4-and-a-half-year-old Caucasian girl was referred to our clinic with a liver biopsy report indicating a diagnosis of glycogen storage disease. Prior to being referred to our clinic, the patient had been under the care of pediatric gastroenterologists. The patient’s initial symptoms included chronic abdominal pain, constipation, and elevated liver transaminase. With the help of the pediatric gastroenterologists, cholestasis, Wilson disease, and autoimmune hepatitis were ruled out. Given that glycogen storage diseases type I and type III are the most common, we initially managed the patient with frequent feedings and a diet that included complex carbohydrates such as a corn starch supplement and a lactose restriction. Following an unfavorable growth velocity and hepatomegaly during the follow-up period, genetic analysis was conducted, which revealed a novel mutation of the phosphorylase kinase regulatory subunit beta gene— a c.C412T (P.Q138x) mutation. As the diagnosis of glycogen storage disease type IX was confirmed, the treatment regimen was altered to a high protein diet (more than 2 g/kg/day) and a low fat diet.
Conclusion Given the mild and varied clinical manifestations of glycogen storage disease type IX, it is possible for the diagnosis to be overlooked. It is important to consider glycogen storage disease type IX in children who present with unexplained hepatomegaly and elevated transaminase levels. Furthermore, due to the distinct management of glycogen storage disease type IX compared with glycogen storage disease type I and glycogen storage disease type III, genetic analysis is essential for an accurate diagnosis.
Keywords Glycogen storage disease type IX, PHKB, Liver, Hepatomegaly, Poor growth. 2024
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Spectrum of Beta-Thalassemia Mutations in PotentialCarriers with Microcytic Hypochromic Anemia from Mazandaranand Golestan, Northern Provinces of Iran
Introduction: β-Thalassaemia is the most common genetic disorder and is considered as a major public health concern in Iran. Different countrywide studies have shown a heterogeneous mutational basis of β-thalassaemia with different frequencies in each area. This study is aimed at investigating the common and rare mutations in Mazandaran and Golestan, northern provinces of Iran. Methods. 5425 microcytic and hypochromic individuals were investigated from Mazandaran and Golestan
provinces. From these, 1323 beta carrier or affected individuals were selected where 938 persons were from Mazandaran and 385 people were from Golestan province, respectively. Result. 53 different mutations were identified, IVSII-1 (G>A) was the most common (59.14%) followed by Cd 22/23/24 (-7 bp) (5.34%), Cd 8 (-AA) (4.93%), Cd30 (G>A) (4.00%), and IVSI-5 (G>C) (3.70%) with a total of 77.11% in Mazandaran Province, respectively. In Golestan Province, IVSI-5 (G>C) was the most
frequent (44.62%) followed by IVSII-1 (G>A) (27.18%), Cd 15 (TGG>TAG) (4.36%), Fr 8/9(+G) (3.85%), and Cd 8(-AA) (2.05%) with a total of 82.06%, respectively. From the 53 different mutations, 22 numbers have been observed in both provinces. Two deletions of the beta gene named Sicilian and Asian-Indian have been detected in Mazandaran with a frequency of 0.72% each. Conclusion. The 53 different mutations identified in this study were the most ever reported mutations
in the country. Due to diversity of different ethnic groups, there are many varieties of mutation in beta globin gene in Iran. It could be assumed that both founder effect and natural selection caused by migration from neighboring areas have complemented each other to produce the high frequency of unique alleles within each region. 2024
The Frequency and Typing of HPV Virus Among Suspected Women Referred to HPV Genotyping Test in Mazandaran, Northern Iran
SUMMARY :
Background: Human papilloma viruses are a group of the Papillomaviridae family (ds DNA viruses), which infect basal epithelial cells. So far, 228 types of HPV have been identified, in which about 40 types infect the genital mu-cosa. In Iran, cervical cancer has been reported as the second most common malignancy in women which is ap-proximately 8.8% of all cancers in women. HPV genotypes are classified as high-risk and low-risk according to cervical cancer. According to previous reports, nearly 70% of cervical cancers occur by HPV genotypes 16 and 18, of which genotype 16 is known as the most prevalent type. The main goal of this study was determining the fre-quency of HPV virus and its genotypes in the female population of Mazandaran. Methods: This study was performed on 91 pathological samples. DNA was extracted from 500 μL of liquid-based cytology samples and PCR was performed for all of the samples. Genotyping step was performed based on strip assay method.
Results: HPV 39 (6.55%), 56 (3.27%), 51 (3.27%), and 68 (3.27%) were the most frequent types respectively. Also, HPV 11 (8.19%) and 6 (3.27%) show the most frequency among LR-HPV genotypes. HPV type 6 (16.39%), 56 (14.75%), 11 (14.75%), 16 (13.11%), and 66 (11.47%) were the four most common types seen in mixed infection samples.
Conclusions: Differences among the types of HPV can be due to various geographical distributions of HPV. Our results revealed HPV 39 (6.55%) is the most common type among of HR-HPV followed by HPV 56, 51, 68 (3.27%); however, HPV 16 and HPV 18 were seen in just one case. HPV 11 (8.19%) and HPV 6 (3.27%) were the most common type among of LR-HPV. 2022
Frequency of PAH Mutations Among Classic Phenylketon Urea Patients in Mazandaran and Golestan Provinces, North of Iran
SUMMARY :
Background: Phenylketonuria (PKU) is the most common aminoacidopathy with an autosomal recessive inheri-tance pattern. A global PKU prevalence is estimated about 6.002 in 100,000 newborns. In Iran, the prevalence of PKU is estimated at about 1 in 4,698, and it shows an increasing trend from north (0.0015%) to south (0.02%) of the country. Untreated PKU causes mental retardation, microcephaly, and seizure. PAH gene mutations located at chromosome 12q23 are responsible for the classical type of this disease. The spectrum of PAH mutations is var-ied in different ethnicities and different parts of the world. The aim of this study was to investigate the frequency of PAH mutation in the Mazandaran province, which could be useful for genetic counseling and prenatal diagno-sis. Methods: A total of 66 individuals from 33 families from two provinces (9 families from Golestan and 24 families from Mazandaran) from north of Iran participated in this study. After genomic DNA extraction, PAH gene analy-sis was carried out using DNA sequencing of both coding and non-coding regions by ABI 3130XL genetic analyz-er.
Results: Twenty-six different mutations were identified in the PAH gene in this study. Four mutations including IVS10-11 (c.1066-11G>A), c.727C>T (p.Arg243X), c.898G>T (p.Ala300Ser), and c.601C>T (p.His201Tyr) were the most common mutations with 37.48% frequency in Mazandaran province. Most frequent mutations in Golestan province were IVSI0-11 (c.1066-11G>A), c.722delG (p.Arg241fs), c.842C>T (p.Pro281Leu), and IVSII+5 (G>A) with frequency 58.57%.
Conclusions: The results from the present study verify heterogeneity of the PAH gene and may help to diagnose tests for carrier detection and prenatal diagnosis of the PKU disease in Iranian population. 2022
Frequencies of CYP2B6∗4,∗5, and ∗6 Alleles within an IranianPopulation (Mazandaran)
Background: -e human CYP2B subfamily consists of one functional gene (CYP2B6) and one pseudogene (CYP2B7P). Cytochrome P450 2B6 (CYP2B6) is a highly polymorphic enzyme that shows marked interindividual and interethnic variations. Currently, 38 alleles have been described, and some of the allelic variants have been associated with low enzyme activity. -e aim of this study was to investigate the frequencies of CYP2B6∗4, CYP2B6∗5, and CYP2B6∗6 alleles in the Mazani
ethnic group among Iranian Population. Methods. -e study was conducted in 289 unrelated healthy volunteers. DNA was extracted from peripheral blood and analyzed by the PCR-RFLP protocol. -e PCR product was digested with restriction enzymes and then separated using agarose gel electrophoresis. Results. -e frequency of CYP2B6∗4, CYP2B6∗5, and CYP2B6∗6 in this study was 34.60%, 7.26%, and 34.54%, respectively. Conclusion. -e frequency of the CYP2B6∗4 allele in the Mazani
ethnic group was much higher (34.60%) than other population. -e frequency of CYP2B6∗6 (34.54%) also was higher than its frequency in other previously reported population. But the frequency of CYP2B6∗5 in this study was lower than expected. -ese results will be useful in understanding the ethnic diversity in Iranian population and offer a preliminary basis for more rational use of drugs that are substrates for CYP2B6 in this population. 2021
GJB2 Gene Related Nonsyndromic Hearing Lossin Mazandaran Province, North of Iran
Abstract :
Introduction: Congenital hearing loss is the most common sensory deficit in the world and mutations in GJB2 gene are the most common cause of deafness in many populations. Frequency of GJB 2 mutations is estimated about 16% in Iran and varies among different provinces with a decreasing trend from north to south. The aim of this study was to investigate the frequency of GJB2 mutations in Mazandaran province, north of Iran, among non-syndromic hearing loss patients. Methods: 262 patients from 204 families participated in this study. After genomic DNA extraction, GJB 2 gene analysis was carried out using DNA sequencing of both coding and non-coding regions by ABI 3130XL genetic analyzer. Results: 30.15% of all subjects showed mutations in GJB2 gene.Four mutations, including c.35delG (Gly12Valfs*), IVSI-1 + 1G > A, c.95G > A (Arg32His) and c.224 G > A (Arg75Gln) comprises 69.89% of all mutations in this study c.35delG and IVSI-1 were the most common mutations among patients respectively. Codon 75 mutation (c.224G > A. p: Arg75Gln) with autosomal dominant inheritance was seen in 7 cases from 3 families. 22 patients showed only one mutation in GJB2 gene and in 126 (48.09%) individuals, parents had a consanguineous marriage. Discussion: Frequency of GJB2 gene related hearing loss among patients was higher than average (16%) in this province. This study also showed a dominant inheritance pattern of GJB2 gene in this area. Consanguineous marriage also showed highly frequent among parents. More investigation needs to clarify cause of hearing loss in those 22 patients with one mutation in GJB2 gene, either two gene inheritance or another gene may be responsible for hearing loss.2020
Laing Early-onset Distal Myopathy Due to the MYH7Mutation in an Iranian Family
Abstract :
Introduction: Laing early-onset distal myopathy is a disorder with autosomal dominant inheritance pattern caused by a mutation in the MYH7 gene that encodes the human β-myosin heavy chain. Most previous studies reported this disorder with mild symptoms involving foot and hand fingers extensors as its early-onset and neck flexors as late-onset symptoms. In this study, the previously reported cases suffered from the same mutation are reviewed, too.
Case Presentation: Our study describes pathological, clinical, imaging, and genetic findings in the first Iranian patient suffering from Laing distal myopathy. The subject is an 8-year-old boy with a moderate phenotype and upper and lower limbs involvement. He also showed a weakness in neck flexors, previously reported in similar cases at early ages. A genetic study was done using the whole exome sequencing method. Next generation sequencing findings revealed a c.4850- 4852AGA deletion (p.k1617del) mutation in MYH7, which previously reported as the cause of Laing distal myopathy. This case is the first indication of Laing distal myopathy from Iran.
Conclusions: Presenting the first Iranian patient with an already known MYH7 mutation associated with Laing distal myopathy will prove the previously reported heterogeneity of this disorder’s phenotype severity, morphological variation, and age of symptoms onset. 2020
Alpha‐globin gene mutation spectrum in patients withmicrocytic hypochromic anemia from Mazandaran Province, Iran
Abstract :
Background: It is estimated about 7% of the world population is carriers of hemoglobin diseases. Alpha‐thalassemia is one of the most common hereditary hemoglobin disorders in the world. This study investigated alpha‐globin mutations in potential carriers with hypochromic and microcytic anemia from Mazandaran, in northern Iran.
Methods: A total of 859 subjects were selected; genomic DNA was extracted and examined for the presence of mutations in the alpha‐globin genes.
Results: Mutation analysis of alpha‐globin genes revealed 27 different mutations. Seven variants were seen in 91.45% of all alpha‐1 and alpha‐2 mutations among patients in this study. The 3.7 kb deletion is the most frequent mutation with a frequency of 49.53%, followed by PolyA2 (15.19%), −4.2 deletion (8.76%), ‐‐MED (5.84%), IVSI‐5nt deletion (5.49%), Hb constant spring (3.62%), and Cd 19 (−G; 3.04%), respectively. There are also seven new variants which were reported for the first time either in alpha‐1 or alpha‐2 genes, including codon 9 (C > A; α2), deletion of codon 60 (AAG deletion; α2), duplication of codon 94‐100 plus 3 base pairs of intron 2 (IVSII + 3; α1), codon 99 (C > A; α2), codon 108(A >G; α2), codon 128 (A > T; α2), and codon 129 (T > G; α2), respectively. The MLPA method also revealed three rare and novel deletions in alpha‐cluster region with about 30 kilobases long.
Conclusion: This study showed an efficient identification of α‐thalassemia can be achieved using standard hematological indices in our population. The details of these variations will help local genetic services for diagnostic and prenatal diagnosis services. 2019
Haplotypes inside the beta-globin gene:use as new biomarkers for beta-thalassemiaprenatal diagnosis in north of Iran
Abstract :
Background: Beta-thalassemia is common in the Mediterranean area as well as the Middle East and India. Official report in Iran revealed the average prevalence rate of carriers about 4%. More than 20 restriction fragment length polymorphisms (RFLPs) are known in the beta-globin gene cluster and used in the prenatal diagnosis(PND) services. Some of these locations may have low allele frequency and are not informative in the prenatal diagnosis. The current study aims to find new haplotypes and polymorphisms with high allele frequency in the local population.
Methods: Two thousand three hundred fifty samples (1,321 male and 1,029 female) from the northern Iran, whom suspected to be the carriers either for alpha or beta thalassemia and referred to the local diagnostic laboratory as a routine services were investigated during five years, (2010–2015). The beta-globin gene was sequenced for all samples.
Results: Heterozygosity for five SNPs in the beta-globin gene was calculated separately.383 individuals (16.29%) showed no sign of nucleotide change in the beta-globin gene sequence. In total, codon2(C/T) 31.72%, IVSII-16 (C/G) 31.72%, IVSII- 74 (G/T) 54.71%, IVSII-81 (C/T) 19.47%,and IVSII-666(T/C)31.72% were seen respectively. Although all five polymorphisms showed reasonably high heterozygosity, IVSII-74 (G/T) [GG wild type (36.5%), G/T (54.71%) and TT (8.8%)] revealed the highest heterozygosity rate. Four combinations of these five SNPs were defined as new haplotypes named M1 to M4. ARMS-PCR also were designed and applied to detect IVSII-74 (G/T) nucleotide position.
Conclusions: This study represents an intragenic polymorphism, IVSII-74, a reliable position with high heterozygosity rates in Iranian population for PND analysis. 2017