Abstract | BACKGROUND: METHODS AND RESULTS: Two brothers, born to consanguineous healthy parents of Arab descent, were evaluated for psychomotor delay associated with triple-A-like syndrome ( anisocoria, alacrima and achalasia). The proband showed markedly increased urinary glycolic acid excretion with normal excretion of oxalate, citrate and glycerate. Abdominal ultrasound showed normal-sized kidneys with normal echotexture. The genetic nature of triple-A-like syndrome in this kindred was found to be unrelated to this metabolic abnormality. Direct DNA sequencing of glycolate oxidase gene (HAO1) revealed a homozygous c.814-1G>C mutation in the invariant -1 position of intron 5 splice acceptor site. Since HAO1 is a liver-specific enzyme, the effect of this novel mutation on splicing was validated by an in vitro hybrid-minigene approach. We confirmed the appearance of an abnormal splice variant in cells transfected with mutant minigene vector. CONCLUSIONS: Our results pinpoint the expression of defective splice variant of glycolate oxidase as the cause of isolated asymptomatic glycolic aciduria. This observation contributes to the development of novel approaches, namely, substrate reduction, for the treatment of primary hyperoxaluria type I.
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Authors | Yaacov Frishberg, Avraham Zeharia, Roman Lyakhovetsky, Ruth Bargal, Ruth Belostotsky |
Journal | Journal of medical genetics
(J Med Genet)
Vol. 51
Issue 8
Pg. 526-9
(Aug 2014)
ISSN: 1468-6244 [Electronic] England |
PMID | 24996905
(Publication Type: Case Reports, Journal Article)
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Copyright | Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. |
Chemical References |
- Glycolates
- Glyoxylates
- glycolic acid
- Alcohol Oxidoreductases
- HAO1 protein, human
- glyoxylic acid
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Topics |
- Adrenal Insufficiency
- Alcohol Oxidoreductases
(genetics)
- Child
- Esophageal Achalasia
- Glycolates
(urine)
- Glyoxylates
(metabolism)
- Humans
- Hyperoxaluria
(etiology, genetics)
- Male
- Metabolism, Inborn Errors
(complications, genetics)
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