The first reported case of Menkes disease caused by an Alu insertion mutation.
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.
Gu
YanHong
Y
Department of Health Policy, National Research Institute for Child Health and Development, 2-10-1 Okura, Tokyo, Japan. gyh@nch.go.jp
Kodama
Hiroko
H
Watanabe
Shigero
S
Kikuchi
Nobuyuki
N
Ishitsuka
Ineo
I
Ozawa
Hiroshi
H
Fujisawa
Chie
C
Shiga
Katsuaki
K
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
D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases