title: Homozygous MAPT R406W mutation causing FTDP phenotype: A unique instance of a unique mutation.
abstract: Frontotemporal dementia is a neurodegenerative disorder among adults. An autosomal-dominantly form of frontotemporal dementia and parkinsonism linked to chromosome 17q21.2 (FTDP-17) was defined in 1996. The MAPT gene is responsible for the major cases of FTDP-17, and tau also has a role in Alzheimer's disease. So far, different FTDP-17 causing mutations have been identified in the MAPT gene. Among different MAPT mutations, the R406W mutation has been reported with a phenotype resembling Alzheimer's disease. Nonetheless, in this study we have identified the first homozygous case of R406W mutation in an Iranian family which shows characteristics of FTDP, just like the other heterozygous mutations of MAPT. This study clearly indicates that homozygous R406W mutation could result in FTDP phenotype. Our family confirms heterogeneity in the clinical phenotype of MAPT mutations; moreover, in the R406W mutation, a dosage effect is likely to contribute to this clinical heterogeneity.
authors.affiliation: Medical Genetics Laboratory of Genome, Isfahan, Iran.
authors.forename: Mahdiyeh
authors.initials: M
authors.lastname: Behnam
authors.affiliation: Isfahan University, Isfahan, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Ghorbani
authors.affiliation: Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
authors.forename: Dae-Seong
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
authors.forename: Hojung
authors.initials: H
authors.lastname: Jang
authors.affiliation: Tohid Genetic Counseling Center, 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: Maryam
authors.initials: M
authors.lastname: Sedghi
authors.affiliation: Division of Genetics and Molecular Biology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mansoor
authors.initials: M
authors.lastname: Salehi
authors.affiliation: Neurology Department, Isfahan Neuroscience Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Behnaz
authors.initials: B
authors.lastname: Ansari
authors.affiliation: Neurology Department, Isfahan Neuroscience Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address: basiri@med.mui.ac.ir.
authors.forename: Keivan
authors.initials: K
authors.lastname: Basiri
mesh_terms: D000328:Adult; D001483:Base Sequence; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D057180:Frontotemporal Dementia / Q000175:diagnosis* / Q000235:genetics; D056726:Genetic Association Studies; D006720:Homozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
keywords: Alzheimer's disease; MAPT; Parkinsonism; frontotemporal dementia