GAA gene mutation detection following clinical evaluation and enzyme activity analysis in Azeri Turkish patients with Po
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ORIGINAL ARTICLE
GAA gene mutation detection following clinical evaluation and enzyme activity analysis in Azeri Turkish patients with Pompe disease Jalal Gharesouran 1,2 & Abbas Jalaiei 3 & Aida Hosseinzadeh 1,2 & Soudeh Ghafouri-Fard 4 & Zeinab Mokhtari 5 & Kazem Ghahremanzadeh 6 & Narges Rezazadeh 7 & Shadi Shiva 8 & Shahram Sadeghvand 8 & Mohammad Taheri 9 Maryam Rezazadeh 2,3
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Received: 28 March 2020 / Accepted: 1 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Pompe disease (PD) is a rare autosomal recessive multi-systemic lysosomal storage disorder, caused by mutations in the acid alpha-glucosidase (GAA) gene located on 17q25.2-q25.3. It is one of about 50 rare genetic diseases categorized as lysosomal storage disorders. This disease is characterized by a range of different symptoms related to acid alpha-glucosidase deficiency. Mutation recognition in the GAA gene can be very significant for purposes such as therapeutic interference, early diagnosis and genotype-phenotype relationship. In the current study, peripheral blood samples were gathered from patients with PD and healthy members of three families. Enzymatic activity of GAA was checked. Then, mutation detection was performed by polymerase chain reaction followed by direct sequencing of all exons in samples with decreased enzyme activity. The identified mutations were investigated using bioinformatics tools to predict possible effects on the protein product and also to compare the mutated sequence with near species. Three novel mutations (c.1966-1968delGAG, c.2011-2012delAT and c.1475-1481dupACCCCAC) were identified in the GAA gene. Assessment of the effects of these mutations on protein structure and function showed the possibility of harmful effects and their significant alterations in the protein structure. The three novel GAA gene mutations detected in this study expand the information about the molecular genetics of PD and can be used to helpdiagnosis and genetic counseling of affected families. Keywords Pompe disease . GAA gene . Novel mutation
Introduction Glycogen storage disease type II (GSD II, OMIM # 232300), also called Pompe disease (PD), is an uncommon autosomal
* Mohammad Taheri [email protected] * Maryam Rezazadeh [email protected] 1
Molecular Genetics Division, GMG center, Tabriz, Iran
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Division of Medical Genetics, Tabriz Children’s Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
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Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
recessive deadly muscle disorder (Schoser et al. 2019), that is caused by acid alpha-glucosidase (GAA acid maltase, EC 3.2.1.20, Swiss-Prot P10253) deficiency due to pathogenic variations in the corresponding GAA gene (GAA, OMIM #
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Alzahra Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
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Children Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
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