title: Use of in silico tools for classification of novel missense mutations identified in dystrophin gene in developing countries.
abstract: DMD gene which is composed of 79 exons is the largest known gene located on X chromosome (Xp21). Point mutations in the dystrophin gene are responsible for 30-35% of cases with DMD/BMD. Mutation analysis of all the exons of the DMD gene is costly in developing countries, therefore, a few of the exons are selected to be analyzed routinely in clinical laboratories. In this study, direct sequencing was used for detection of point mutations in 10 exons of dystrophin gene in patients affected with DMD without detectable large rearrangements. Freely available programs were used to predict the damaging effects of the mutations. Point mutations were successfully detected in three patients. Three novel mutations, two missense mutations located on nonconservative domains and a single nucleotide deletion, were detected. Missense mutations were predicted to change splicing efficiency. Detection of point mutations by DNA analysis followed by prediction of the pathogenecity by using bioinformatic tool might be an asset to provide proper diagnosis or genetic counseling to patients and their family.
authors.affiliation: Pediatric Inherited Disease Research Center (PIDRC), Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Narges
authors.initials: N
authors.lastname: Nouri
authors.affiliation: Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Esmat
authors.initials: E
authors.lastname: Fazel-Najafabadi
authors.affiliation: Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mahdieh
authors.initials: M
authors.lastname: Behnam
authors.affiliation: Pediatric Inherited Disease Research Center (PIDRC), Isfahan University of Medical Sciences, Isfahan, Iran; Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Nayereh
authors.initials: N
authors.lastname: Nouri
authors.affiliation: Department of Genetics, Especial Medical Center, Tehran, Iran.
authors.forename: Omid
authors.initials: O
authors.lastname: Aryani
authors.affiliation: Department of Neurology, Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Ghasemi
authors.affiliation: Department of Pediatrics, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Jafar
authors.initials: J
authors.lastname: Nasiri
authors.affiliation: Pediatric Inherited Disease Research Center (PIDRC), Isfahan University of Medical Sciences, Isfahan, Iran; Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address: m_sedghi@azh.mui.ac.ir.
authors.forename: Maryam
authors.initials: M
authors.lastname: Sedghi
mesh_terms: D000465:Algorithms; D000483:Alleles; D000595:Amino Acid Sequence; D003198:Computer Simulation; D016384:Consensus Sequence; D004252:DNA Mutational Analysis; D003906:Developing Countries; D016189:Dystrophin / Q000737:chemistry / Q000235:genetics*; D005091:Exons; D006801:Humans; D008297:Male; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis* / Q000235:genetics*; D020125:Mutation, Missense; D056510:Position-Specific Scoring Matrices; D011379:Prognosis; D016415:Sequence Alignment
chemical_list: D016189:Dystrophin
keywords: BMD; Becker muscular dystrophy; Bioinformatics; DMD; Direct sequencing; Duchenne muscular dystrophy; ESE; Exonic Splicing Enhancer; HSF; Human Splicing Finder; MLPA; Missense mutation; Multiplex Ligation-dependent Probe Amplification; Panther; PolyPhen; Polymorphism Phenotyping; Protein ANalysis THrough Evolutionary Relationships; SIFT; SNAP; Sorting Intolerant From Tolerant; screening for non-acceptable polymorphisms