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Mohammad Ali Faghihi - One of the best experts on this subject based on the ideXlab platform.
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A novel Splice Site Mutation in WAS gene in patient with Wiskott-Aldrich syndrome and chronic colitis: a case report
BMC Medical Genetics, 2018Co-Authors: Hossein Esmaeilzadeh, Hassan Dastsooz, Mohammad Reza Bordbar, Mohammad Silawi, Mohammad Ali Farazi Fard, Ali Adib, Ali Kafashan, Zahra Tabatabaei, Forough Sadeghipour, Mohammad Ali FaghihiAbstract:Background Wiskott-Aldrich syndrome is an X-linked recessive immunodeficiency due to Mutations in Wiskott-Aldrich syndrome ( WAS ) gene. WAS gene is encoded for a multifunctional protein with key roles in actin polymerization, signaling pathways, and cytoskeletal rearrangement. Therefore, the impaired protein or its absence cause phenotypic spectrum of the disease. Since identification of novel Mutations in WAS gene can help uncover the exact pathogenesis of Wiskott-Aldrich syndrome, the purpose of this study was to investigate disease causing-Mutation in an Iranian male infant suspicious of this disorder. Case presentation The patient had persistent thrombocytopenia from birth, sepsis, and recurrent gastrointestinal bleeding suggestive of both Wiskott-Aldrich syndrome and chronic colitis in favor of inflammatory bowel disease (IBD). To find mutated gene in the proband, whole exome sequencing was performed for the patient and its data showed a novel, private, hemizygous Splice Site Mutation in WAS gene (c.360 + 1G > C). Conclusions Our study found a novel, Splice-Site Mutation in WAS gene and help consider the genetic counselling more precisely for families with clinical phenotypes of both Wiskott-Aldrich syndrome and inflammatory bowel disease and may suggest linked pathways between these two diseases.
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Glycogen storage disease IIIa: A private homozygous Splice Site Mutation in AGL gene
Gene Reports, 2017Co-Authors: Amir Anushiravani, Mohammad Ali Faghihi, Hassan Dastsooz, Kamran Bagheri LankaraniAbstract:Abstract Background Glycogen storage disease III (GSD III) is an autosomal recessive metabolic disorder due to disease-causing Mutations in amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL), the gene encoding glycogen debrancher enzyme (GDE). GSD III is usually presented with clinical findings of liver, cardiac muscle, and skeletal muscle. The purpose of this study was to report a 43-year-old Iranian patient affected by a GSD IIIa who had muscle weakness and hepatic and cardiac abnormalities. Materials and methods To find the genetic cause of this familial case of GSD, whole exome sequencing utilizing next generation sequencing on an Illumina platform was performed on DNA sample from the proband. In addition, to confirm a novel identified Mutation in this patient, Sanger sequencing was carried out using both forward and reverse primers. Moreover, different bioinformatics software and database were used to predict the pathogenicity of this Mutation. Results A homozygous Splice-Site Mutation in AGL gene (NM_000642.2: c.3837-1G > A) in the patient affected by GSD type IIIa was identified. Using Sanger sequencing, this new Mutation was confirmed as homozygous state in the proband. Moreover, this Mutation has not been identified in all database and our database, namely BayanGene which represents data of around 500 whole exome sequencing of Iranian Individuals. Conclusions A deleterious Splice Site Mutation in AGL gene was identified in our patient and adds to many other previous reports and extends the spectrum of GSD IIIa. Such reports help confirm the diagnosis of the disease and to perform accurate genetic counselling for their family members.
Wasim Ahmad - One of the best experts on this subject based on the ideXlab platform.
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A novel Splice Site Mutation in gene C2orf37 underlying Woodhouse–Sakati syndrome (WSS) in a consanguineous family of Pakistani origin
Gene, 2011Co-Authors: Rabia Habib, Saadullah Khan, Muhammad Nasim Khan, Sulman Basit, Wasim AhmadAbstract:Abstract Woodhouse–Sakati Syndrome (WSS) is a rare autosomal recessive multisystemic disorder that is marked by hypogonadism, alopecia, intellectual disability, deafness, diabetes mellitus and progressive extrapyramidal defects. Mutations in the gene C2orf37 are the cause of Woodhouse–Sakati syndrome. In the present study, a four-generation consanguineous family with clinical manifestations of WSS was ascertained from a remote region of Pakistan. Linkage in the family was tested using microsatellite markers linked to several genes involved in producing WSS related phenotypes. Linkage in the family was established to the gene C2orf37, mapped on chromosome 2q22.3–2q35. DNA sequence analysis revealed a novel Splice Site Mutation involving a homozygous G → A transition in the Splice donor Site of intron 3 (c.321 + 1 G > A) of C2orf37. This study presents a first report of Woodhouse–Sakati syndrome identified in Pakistani population.
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A novel Splice Site Mutation in gene C2orf37 underlying Woodhouse-Sakati syndrome (WSS) in a consanguineous family of Pakistani origin.
Gene, 2011Co-Authors: Rabia Habib, Saadullah Khan, Muhammad Nasim Khan, Sulman Basit, Wasim AhmadAbstract:Woodhouse-Sakati Syndrome (WSS) is a rare autosomal recessive multisystemic disorder that is marked by hypogonadism, alopecia, intellectual disability, deafness, diabetes mellitus and progressive extrapyramidal defects. Mutations in the gene C2orf37 are the cause of Woodhouse-Sakati syndrome. In the present study, a four-generation consanguineous family with clinical manifestations of WSS was ascertained from a remote region of Pakistan. Linkage in the family was tested using microsatellite markers linked to several genes involved in producing WSS related phenotypes. Linkage in the family was established to the gene C2orf37, mapped on chromosome 2q22.3-2q35. DNA sequence analysis revealed a novel Splice Site Mutation involving a homozygous G→A transition in the Splice donor Site of intron 3 (c.321+1G>A) of C2orf37. This study presents a first report of Woodhouse-Sakati syndrome identified in Pakistani population.
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a novel Splice Site Mutation in the cdh3 gene in hypotrichosis with juvenile macular dystrophy
Clinical and Experimental Dermatology, 2009Co-Authors: Musharraf Jelani, Salman M Chishti, Wasim AhmadAbstract:BACKGROUND: Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive disorder characterized by sparse hair on the scalp and early blindness. Mutations in the CDH3 gene have been reported to underlie HJMD. AIM: To identify a gene responsible for HJMD in a large, four-generation Pakistani family. METHODS: Genotyping of 13 members of the family, including 6 affected and 7 unaffected members, was carried out using polymorphic microsatellite markers closely linked to the CDH3 on chromosome 16q22.1. To screen for Mutations in the CDH3 gene, all of its exons and Splice junctions were amplified using PCR from genomic DNA and sequenced directly, using an automated DNA sequencer. RESULTS: Microsatellite analysis showed linkage of the family to the CDH3 gene on chromosome 16q22.1. Sequence analysis of the CDH3 gene revealed a novel Splice-Site Mutation (IVS10-1 G-->T), leading to probable skipping of exon 11 and a shift in the reading frame. CONCLUSION: The Mutation identified here represents the first Mutation in the CDH3 gene causing HJMD in a Pakistani population.
Wolfgang Kerner - One of the best experts on this subject based on the ideXlab platform.
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a homozygous hfe gene Splice Site Mutation ivs5 1 g a in a hereditary hemochromatosis patient of vietnamese origin
Gastroenterology, 2002Co-Authors: Michael Steiner, K Ocran, Janine Genschel, Patrick Meier, H Gerl, Michael Ventz, Marieluise Schneider, Carsten Buttner, Kamilla Wadowska, Wolfgang KernerAbstract:Abstract The vast majority of Caucasian patients presenting with hereditary hemochromatosis demonstrate a single homozygous missense Mutation in the HFE gene (C282Y). The underlying genetic defects in hemochromatosis patients of non-Caucasian origin are largely unknown. A 48-year-old man of Vietnamese origin presented with insulin-dependent diabetes mellitus, tertiary adrenocortical insufficiency, and laboratory results highly indicative of hereditary hemochromatosis. Because the patient was negative for the known HFE gene Mutations C282Y, H63D, and S65C HFE, the entire coding region and intron/exon boundaries of the HFE gene was investigated. Sequencing studies identified a homozygous G-to-A transition at position +1 of intron 5 (IVS5+1 G/A). This newly described Mutation alters the invariant G at position +1 of the 5' Splice Site causing altered mRNA splicing and exon skipping with exon 4 being Spliced to exon 6. Both heterozygously affected children (age 19 and 20 years) had moderately increased ferritin levels with normal serum iron concentration and transferrin saturation. The newly described Mutation was not detected in a control group consisting of 220 Caucasian individuals as verified by allele-specific polymerase chain reaction. We describe for the first time a homozygous HFE Splice Site Mutation (IVS5+1 G/A) in a non-Caucasian patient with hereditary hemochromatosis. Although the absence of this novel HFE gene Mutation in Caucasian subjects suggests that the Mutation is exclusive to this family, Mutation screening in populations of different ethnic background is recommended to precisely define its contribution to hereditary hemochromatosis in non-Caucasian patients. GASTROENTEROLOGY 2002;122:789-795
Michael Steiner - One of the best experts on this subject based on the ideXlab platform.
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Hemochromatosis (HFE) gene Splice Site Mutation IVS5+1 G/A in North American Vietnamese with and without phenotypic evidence of iron overload
Translational Research, 2007Co-Authors: Michael Steiner, Catherine Leiendecker-foster, Gordon D. Mclaren, Beverly M. Snively, Christine E. Mclaren, Paul C. Adams, John H. EckfeldtAbstract:Homozygosity for a novel hemochromatosis ( HFE ) gene Splice Site Mutation (IVS5+1 G/A) was previously reported in a 48-year-old Vietnamese man residing in Germany who had an elevated serum ferritin (SF) and transferrin saturation (TS) and severe iron overload on liver biopsy. This Mutation was not found in 222 controls of central European origin but has been found in Southeast Asians living in Vietnam without evidence of iron overload. Hemochromatosis and iron overload screening (HEIRS) Study is an ongoing, multiethnic, primary care-based study of 101,168 North American adults, including 12,772 Asians, a group that the HEIRS Study found has a significantly higher than expected prevalence of elevated serum TS and SF but very low prevalence of the common C282Y and H63D HFE alleles usually associated with hereditary hemochromatosis. It was hypothesized that the IVS5+1 G/A Splice Site Mutation might explain some elevated biochemical iron measures in North American Asians. Overall, 200 Vietnamese subjects from the Los Angeles Field Center who had TS and SF values greater than the 75th percentile of all HEIRS Study participants after adjusting for covariates and 149 controls randomly selected to represent this Vietnamese population were genotyped. Among cases, 1 homozygous mutant and 7 heterozygotes were found; among controls, 1 homozygous mutant and 4 heterozygotes were found yielding an allele frequency of 2.32% for cases and 2.04% for controls ( P > 0.5). This finding suggests that the HFE IVS5+1 G/A Splice Site Mutation is not the major explanation for unexpectedly high prevalence of TS and SF in North American Asians.
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a homozygous hfe gene Splice Site Mutation ivs5 1 g a in a hereditary hemochromatosis patient of vietnamese origin
Gastroenterology, 2002Co-Authors: Michael Steiner, K Ocran, Janine Genschel, Patrick Meier, H Gerl, Michael Ventz, Marieluise Schneider, Carsten Buttner, Kamilla Wadowska, Wolfgang KernerAbstract:Abstract The vast majority of Caucasian patients presenting with hereditary hemochromatosis demonstrate a single homozygous missense Mutation in the HFE gene (C282Y). The underlying genetic defects in hemochromatosis patients of non-Caucasian origin are largely unknown. A 48-year-old man of Vietnamese origin presented with insulin-dependent diabetes mellitus, tertiary adrenocortical insufficiency, and laboratory results highly indicative of hereditary hemochromatosis. Because the patient was negative for the known HFE gene Mutations C282Y, H63D, and S65C HFE, the entire coding region and intron/exon boundaries of the HFE gene was investigated. Sequencing studies identified a homozygous G-to-A transition at position +1 of intron 5 (IVS5+1 G/A). This newly described Mutation alters the invariant G at position +1 of the 5' Splice Site causing altered mRNA splicing and exon skipping with exon 4 being Spliced to exon 6. Both heterozygously affected children (age 19 and 20 years) had moderately increased ferritin levels with normal serum iron concentration and transferrin saturation. The newly described Mutation was not detected in a control group consisting of 220 Caucasian individuals as verified by allele-specific polymerase chain reaction. We describe for the first time a homozygous HFE Splice Site Mutation (IVS5+1 G/A) in a non-Caucasian patient with hereditary hemochromatosis. Although the absence of this novel HFE gene Mutation in Caucasian subjects suggests that the Mutation is exclusive to this family, Mutation screening in populations of different ethnic background is recommended to precisely define its contribution to hereditary hemochromatosis in non-Caucasian patients. GASTROENTEROLOGY 2002;122:789-795
Hossein Esmaeilzadeh - One of the best experts on this subject based on the ideXlab platform.
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A novel Splice Site Mutation in WAS gene in patient with Wiskott-Aldrich syndrome and chronic colitis: a case report
BMC Medical Genetics, 2018Co-Authors: Hossein Esmaeilzadeh, Hassan Dastsooz, Mohammad Reza Bordbar, Mohammad Silawi, Mohammad Ali Farazi Fard, Ali Adib, Ali Kafashan, Zahra Tabatabaei, Forough Sadeghipour, Mohammad Ali FaghihiAbstract:Background Wiskott-Aldrich syndrome is an X-linked recessive immunodeficiency due to Mutations in Wiskott-Aldrich syndrome ( WAS ) gene. WAS gene is encoded for a multifunctional protein with key roles in actin polymerization, signaling pathways, and cytoskeletal rearrangement. Therefore, the impaired protein or its absence cause phenotypic spectrum of the disease. Since identification of novel Mutations in WAS gene can help uncover the exact pathogenesis of Wiskott-Aldrich syndrome, the purpose of this study was to investigate disease causing-Mutation in an Iranian male infant suspicious of this disorder. Case presentation The patient had persistent thrombocytopenia from birth, sepsis, and recurrent gastrointestinal bleeding suggestive of both Wiskott-Aldrich syndrome and chronic colitis in favor of inflammatory bowel disease (IBD). To find mutated gene in the proband, whole exome sequencing was performed for the patient and its data showed a novel, private, hemizygous Splice Site Mutation in WAS gene (c.360 + 1G > C). Conclusions Our study found a novel, Splice-Site Mutation in WAS gene and help consider the genetic counselling more precisely for families with clinical phenotypes of both Wiskott-Aldrich syndrome and inflammatory bowel disease and may suggest linked pathways between these two diseases.
