title: A loss-of-function mutation in the SLC9A6 gene causes X-linked mental retardation resembling Angelman syndrome.
abstract: SLC9A6 mutations have been reported in families in whom X-linked mental retardation (XMR) mimics Angelman syndrome (AS). However, the relative importance of SLC9A6 mutations in patients with an AS-like phenotype or XMR has not been fully investigated. Here, the involvement of SLC9A6 mutations in 22 males initially suspected to have AS but found on genetic testing not to have AS (AS-like cohort), and 104 male patients with XMR (XMR cohort), was investigated. A novel SLC9A6 mutation (c.441delG, p.S147fs) was identified in one patient in the AS-like cohort, but no mutation was identified in XMR cohort, suggesting mutations in SLC9A6 are not a major cause of the AS-like phenotype or XMR. The patient with the SLC9A6 mutation showed the typical AS phenotype, further demonstrating the similarity between patients with AS and those with SLC9A6 mutations. To clarify the effect of the SLC9A6 mutation, we performed RT-PCR and Western blot analysis on lymphoblastoid cells from the patient. Expression of the mutated transcript was significantly reduced, but was restored by cycloheximide treatment, indicating the presence of nonsense mediated mRNA decay. Western blot analysis demonstrated absence of the normal NHE6 protein encoded for by SLC9A6. Taken together, these findings indicate a loss-of-function mutation in SLC9A6 caused the phenotype in our patient.
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Kana
authors.initials: K
authors.lastname: Hosoki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsushita
authors.forename: Makoto
authors.initials: M
authors.lastname: Funatsuka
authors.forename: Kayoko
authors.initials: K
authors.lastname: Saito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanazawa
authors.forename: Yu-Ichi
authors.initials: Y
authors.lastname: Goto
authors.forename: Shinji
authors.initials: S
authors.lastname: Saitoh
mesh_terms: D000595:Amino Acid Sequence; D017204:Angelman Syndrome / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D004252:DNA Mutational Analysis; D015536:Down-Regulation / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D059365:Nonsense Mediated mRNA Decay / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D050505:Mutant Proteins; D012333:RNA, Messenger; C445316:SLC9A6 protein, human; D017923:Sodium-Hydrogen Exchangers