Title
Complete genomic structure and mutational spectrum of PHKA2 in patients with X-linked liver glycogenosis type I and II Complete genomic structure and mutational spectrum of PHKA2 in patients with X-linked liver glycogenosis type I and II
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
New York, N.Y. ,
Subject
Human medicine
Source (journal)
The American journal of human genetics. - New York, N.Y.
Volume/pages
64(1999) :6 , p. 1541-1549
ISSN
0002-9297
ISI
000080696200006
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
X-linked liver glycogenosis (XLG) is probably the most frequent glycogen-storage disease. XLG can be divided into two subtypes: XLG I, with a deficiency in phosphorylase kinase (PHK) activity in peripheral blood cells and liver; and XLG II, with normal in vitro PHK activity in peripheral blood cells and with variable activity in liver. Both types of XLG are caused by mutations in the same gene, PHKA2, that encodes the regulatory alpha subunit of PHK. To facilitate mutation analysis in PHKA2, we determined its genomic structure. The gene consists of 33 exons, spanning greater than or equal to 65 kb. By SSCP analysis of the different PHKA2 exons, we identified five new XLG I mutations, one new XLG II mutation, and one mutation present in both a patient with XLG I and a patient with XLG IT, bringing the total to 19 XLG I and 12 XLG II mutations. Most XLG I mutations probably lead to truncation or disruption of the PHKA2 protein. In contrast, all XLG II mutations are missense mutations or small in-frame deletions and insertions. These results suggest that the biochemical differences between XLG I and XLG TT might be due to the different nature of the disease-causing mutations in PHKA2. XLG I mutations may lead to absence of the alpha subunit, which causes an unstable PHK holoenzyme and deficient enzyme activity, whereas XLG II mutations may lead to in vivo deregulation of PHK, which might be difficult to demonstrate in vitro.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/5e6d55/5629.pdf
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