title: De novo WDR45 mutation in a patient showing clinically Rett syndrome with childhood iron deposition in brain.
abstract: Rett syndrome (RTT) is a neurodevelopmental disorder mostly caused by MECP2 mutations. We identified a de novo WDR45 mutation, which caused a subtype of neurodegeneration with brain iron accumulation, in a patient showing clinically typical RTT. The mutation (c.830+1G>A) led to aberrant splicing in lymphoblastoid cells. Sequential brain magnetic resonance imaging demonstrated that iron deposition in the globus pallidus and the substantia nigra was observed as early as at 11 years of age. Because the patient showed four of the main RTT diagnostic criteria, WDR45 should be investigated in patients with RTT without MECP2 mutations.
authors.affiliation: 1] Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan [2] Department of Clinical Neurology and Stroke Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Ohba
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Nabatame
authors.affiliation: Division of Pediatrics, Osaka Developmental Rehabilitation Center, Osaka, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Iijima
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Nishiyama
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Department of Clinical Neurology and Stroke Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ozono
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D000293:Adolescent; D000483:Alleles; D017398:Alternative Splicing; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D009154:Mutation; D015518:Rett Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C578284:WDR45 protein, human; D007501:Iron