GAA gene mutation detection following clinical evaluation and enzyme activity analysis in Azeri Turkish patients with Pompe disease
Autor: | Mohammad Taheri, Maryam Rezazadeh, Kazem Ghahremanzadeh, Soudeh Ghafouri-Fard, Shahram Sadeghvand, Narges Rezazadeh, Jalal Gharesouran, Abbas Jalaiei, Zeinab Mokhtari, Shadi Shiva, Aida Hosseinzadeh |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty Adolescent Turkey Genetic counseling DNA Mutational Analysis Disease Biology Gene mutation medicine.disease_cause Biochemistry law.invention 03 medical and health sciences Cellular and Molecular Neuroscience Exon 0302 clinical medicine law Molecular genetics medicine Humans Genetic Predisposition to Disease Child Gene Polymerase chain reaction Genetics Mutation Glycogen Storage Disease Type II Infant alpha-Glucosidases 030104 developmental biology Child Preschool Female Neurology (clinical) Glycogen 030217 neurology & neurosurgery |
Zdroj: | Metabolic Brain Disease. 35:1127-1134 |
ISSN: | 1573-7365 0885-7490 |
Popis: | 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. |
Databáze: | OpenAIRE |
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