Silent exonic mutation in the acid-alpha-glycosidase gene that causes glycogen storage disease type II by affecting mRNA splicing.
Glycogen-storage disease type II (GSDII) is an autosomal recessive disorder caused by a deficiency of acid alpha-glucosidase (GAA). The residual GAA activity is largely related to the severity of the clinical course. Most patients with infantile-onset GSDII do not show any enzyme activity, whereas patients with the late-onset forms of GSDII show various degrees of GAA activity. We performed a molecular genetic study on a Japanese boy with childhood-onset GSDII. The patient was a compound heterozygote for a newly discovered splice-site c.546G>T mutation and a recurrent missense p.R600C mutation, which usually causes the fatal infantile form in a homozygous state. The c.546G>T mutation, which did not alter the amino-acid sequence, was positioned at the last base of exon 2. cDNA-sequencing analysis revealed that c.546G>T was a leaky splice mutation, leading to the production of a normally spliced transcript, which was responsible for the low-level (approximately 10%) expression of the active enzyme in the patient's fibroblasts.
Maimaiti
Mireguli
M
Department of Pediatrics, Asahikawa Medical College, Asahikawa, Hokkaido, Japan.
Takahashi
Satoru
S
Okajima
Kazuki
K
Suzuki
Nao
N
Ohinata
Junko
J
Araki
Akiko
A
Tanaka
Hajime
H
Mukai
Tokuo
T
Fujieda
Kenji
K
D017668:Age of Onset; D002648:Child; D017931:DNA Primers / Q000737:chemistry / Q000235:genetics; D005091:Exons / Q000235:genetics*; D005347:Fibroblasts / Q000201:enzymology; D006009:Glycogen Storage Disease Type II / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007564:Japan; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D000520:alpha-Glucosidases / Q000235:genetics*
D017931:DNA Primers; C509951:GAA protein, human; D000520:alpha-Glucosidases