title: The first reported case of Menkes disease caused by an Alu insertion mutation.
abstract: We present the first reported case of Menkes disease caused by an Alu element insertion mutation that interfered with splicing regulatory elements. A whole young AluYa5a2 element, which was 382-bp long, was identified within exon 9 of the ATP7A gene, and all of exon 9 was aberrantly skipped in the cDNA, resulting in severely truncated proteins. To confirm whether the aberrant skipping resulted in Alu insertion, an exonic splicing enhancer finder was used. The Alu element created two new high-score exonic splicing enhancer sequences in the mutation located near the site of the insertion. Exon 9, which encodes the first and second transmembrane domains, is necessary for the normal function of the ATP7A protein.
authors.affiliation: Department of Health Policy, National Research Institute for Child Health and Development, 2-10-1 Okura, Tokyo, Japan. gyh@nch.go.jp
authors.forename: YanHong
authors.initials: Y
authors.lastname: Gu
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kodama
authors.forename: Shigero
authors.initials: S
authors.lastname: Watanabe
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kikuchi
authors.forename: Ineo
authors.initials: I
authors.lastname: Ishitsuka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ozawa
authors.forename: Chie
authors.initials: C
authors.lastname: Fujisawa
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Shiga
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D020087:Alu Elements / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics*; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis; D005091:Exons; D006801:Humans; D007223:Infant; D008297:Male; D007706:Menkes Kinky Hair Syndrome / Q000235:genetics*; D009154:Mutation
chemical_list: D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases