Loading…
Mutations in the glucose-6-phosphatase gene are associated with glycogen storage disease types 1a and 1aSP but not 1b and 1c
Glycogen storage disease (GSD) type 1, which is caused by the deficiency of glucose-6-phosphatase (G6Pase), is an autosomal recessive disease with heterogenous symptoms. Two models of G6Pase catalysis have been proposed to explain the observed heterogeneities. The translocase-catalytic unit model pr...
Saved in:
Published in: | The Journal of clinical investigation 1995-01, Vol.95 (1), p.234-240 |
---|---|
Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c369t-e2e0cb03ddadf9ee82b94adb5354ec28102887789a85a0575b777308c094f1b93 |
---|---|
cites | |
container_end_page | 240 |
container_issue | 1 |
container_start_page | 234 |
container_title | The Journal of clinical investigation |
container_volume | 95 |
creator | Lei, K J Shelly, L L Lin, B Sidbury, J B Chen, Y T Nordlie, R C Chou, J Y |
description | Glycogen storage disease (GSD) type 1, which is caused by the deficiency of glucose-6-phosphatase (G6Pase), is an autosomal recessive disease with heterogenous symptoms. Two models of G6Pase catalysis have been proposed to explain the observed heterogeneities. The translocase-catalytic unit model proposes that five GSD type 1 subgroups exist which correspond to defects in the G6Pase catalytic unit (1a), a stabilizing protein (1aSP), the glucose-6-P (1b), phosphate/pyrophosphate (1c), and glucose (1d) translocases. Conversely, the conformation-substrate-transport model suggests that G6Pase is a single multifunctional membrane channel protein possessing both catalytic and substrate (or product) transport activities. We have recently demonstrated that mutations in the G6Pase catalytic unit cause GSD type 1a. To elucidate whether mutations in the G6Pase gene are responsible for other GSD type 1 subgroups, we characterized the G6Pase gene of GSD type 1b, 1c, and 1aSP patients. Our results show that the G6Pase gene of GSD type 1b and 1c patients is normal, consistent with the translocase-catalytic unit model of G6Pase catalysis. However, a mutation in exon 2 that converts an Arg at codon 83 to a Cys (R83C) was identified in both G6Pase alleles of the type 1aSP patient. The R83C mutation was also demonstrated in one homozygous and five heterogenous GSD type 1a patients, indicating that type 1aSP is a misclassification of GSD type 1a. We have also analyzed the G6Pase gene of seven additional type 1a patients and uncovered two new mutations that cause GSD type 1a. |
doi_str_mv | 10.1172/JCI117645 |
format | article |
fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_295414</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>7814621</sourcerecordid><originalsourceid>FETCH-LOGICAL-c369t-e2e0cb03ddadf9ee82b94adb5354ec28102887789a85a0575b777308c094f1b93</originalsourceid><addsrcrecordid>eNpVkE9LAzEQxXNQaq0e_ABCrh5Wk93sJjl4kOKfSkVBPS-zyWx3pd0sm1Qp-OFNqRQ9DA_mvd8MPELOOLvkXKZXj9NZ1ELkB2TMWMoTLTN1RI69_2CMC5GLERlJxUWR8jH5floHCK3rPG07Ghqki-XaOI9JkfSN830DAXzcYocUhjjeO9NCQEu_2tDE-Ma46FIf3AALpLb1uCXCpkdPOVDobJTXF1qtA-1coLza7cwJOaxh6fH0Vyfk_e72bfqQzJ_vZ9ObeWKyQocEU2SmYpm1YGuNqNJKC7BVnuUCTao4S5WSUmlQObBc5pWUMmPKMC1qXulsQq53d_t1tUJrsAsDLMt-aFcwbEoHbfnf6dqmXLjPMtW54CLyFzveDM77Aes9ylm5Lb3clx6z539_7ZO_jWc_ZcSAEA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Mutations in the glucose-6-phosphatase gene are associated with glycogen storage disease types 1a and 1aSP but not 1b and 1c</title><source>EZB Free E-Journals</source><source>PubMed Central</source><creator>Lei, K J ; Shelly, L L ; Lin, B ; Sidbury, J B ; Chen, Y T ; Nordlie, R C ; Chou, J Y</creator><creatorcontrib>Lei, K J ; Shelly, L L ; Lin, B ; Sidbury, J B ; Chen, Y T ; Nordlie, R C ; Chou, J Y</creatorcontrib><description>Glycogen storage disease (GSD) type 1, which is caused by the deficiency of glucose-6-phosphatase (G6Pase), is an autosomal recessive disease with heterogenous symptoms. Two models of G6Pase catalysis have been proposed to explain the observed heterogeneities. The translocase-catalytic unit model proposes that five GSD type 1 subgroups exist which correspond to defects in the G6Pase catalytic unit (1a), a stabilizing protein (1aSP), the glucose-6-P (1b), phosphate/pyrophosphate (1c), and glucose (1d) translocases. Conversely, the conformation-substrate-transport model suggests that G6Pase is a single multifunctional membrane channel protein possessing both catalytic and substrate (or product) transport activities. We have recently demonstrated that mutations in the G6Pase catalytic unit cause GSD type 1a. To elucidate whether mutations in the G6Pase gene are responsible for other GSD type 1 subgroups, we characterized the G6Pase gene of GSD type 1b, 1c, and 1aSP patients. Our results show that the G6Pase gene of GSD type 1b and 1c patients is normal, consistent with the translocase-catalytic unit model of G6Pase catalysis. However, a mutation in exon 2 that converts an Arg at codon 83 to a Cys (R83C) was identified in both G6Pase alleles of the type 1aSP patient. The R83C mutation was also demonstrated in one homozygous and five heterogenous GSD type 1a patients, indicating that type 1aSP is a misclassification of GSD type 1a. We have also analyzed the G6Pase gene of seven additional type 1a patients and uncovered two new mutations that cause GSD type 1a.</description><identifier>ISSN: 0021-9738</identifier><identifier>DOI: 10.1172/JCI117645</identifier><identifier>PMID: 7814621</identifier><language>eng</language><publisher>United States</publisher><subject>Alleles ; Amino Acid Sequence ; Base Sequence ; Cells, Cultured ; Cloning, Molecular ; Genome, Human ; Glucose-6-Phosphatase - genetics ; Glycogen Storage Disease Type I - classification ; Glycogen Storage Disease Type I - enzymology ; Glycogen Storage Disease Type I - genetics ; Heterozygote ; Homozygote ; Humans ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutation - genetics ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Transfection</subject><ispartof>The Journal of clinical investigation, 1995-01, Vol.95 (1), p.234-240</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c369t-e2e0cb03ddadf9ee82b94adb5354ec28102887789a85a0575b777308c094f1b93</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC295414/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC295414/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7814621$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lei, K J</creatorcontrib><creatorcontrib>Shelly, L L</creatorcontrib><creatorcontrib>Lin, B</creatorcontrib><creatorcontrib>Sidbury, J B</creatorcontrib><creatorcontrib>Chen, Y T</creatorcontrib><creatorcontrib>Nordlie, R C</creatorcontrib><creatorcontrib>Chou, J Y</creatorcontrib><title>Mutations in the glucose-6-phosphatase gene are associated with glycogen storage disease types 1a and 1aSP but not 1b and 1c</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>Glycogen storage disease (GSD) type 1, which is caused by the deficiency of glucose-6-phosphatase (G6Pase), is an autosomal recessive disease with heterogenous symptoms. Two models of G6Pase catalysis have been proposed to explain the observed heterogeneities. The translocase-catalytic unit model proposes that five GSD type 1 subgroups exist which correspond to defects in the G6Pase catalytic unit (1a), a stabilizing protein (1aSP), the glucose-6-P (1b), phosphate/pyrophosphate (1c), and glucose (1d) translocases. Conversely, the conformation-substrate-transport model suggests that G6Pase is a single multifunctional membrane channel protein possessing both catalytic and substrate (or product) transport activities. We have recently demonstrated that mutations in the G6Pase catalytic unit cause GSD type 1a. To elucidate whether mutations in the G6Pase gene are responsible for other GSD type 1 subgroups, we characterized the G6Pase gene of GSD type 1b, 1c, and 1aSP patients. Our results show that the G6Pase gene of GSD type 1b and 1c patients is normal, consistent with the translocase-catalytic unit model of G6Pase catalysis. However, a mutation in exon 2 that converts an Arg at codon 83 to a Cys (R83C) was identified in both G6Pase alleles of the type 1aSP patient. The R83C mutation was also demonstrated in one homozygous and five heterogenous GSD type 1a patients, indicating that type 1aSP is a misclassification of GSD type 1a. We have also analyzed the G6Pase gene of seven additional type 1a patients and uncovered two new mutations that cause GSD type 1a.</description><subject>Alleles</subject><subject>Amino Acid Sequence</subject><subject>Base Sequence</subject><subject>Cells, Cultured</subject><subject>Cloning, Molecular</subject><subject>Genome, Human</subject><subject>Glucose-6-Phosphatase - genetics</subject><subject>Glycogen Storage Disease Type I - classification</subject><subject>Glycogen Storage Disease Type I - enzymology</subject><subject>Glycogen Storage Disease Type I - genetics</subject><subject>Heterozygote</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Site-Directed</subject><subject>Mutation - genetics</subject><subject>Polymerase Chain Reaction</subject><subject>Sequence Analysis, DNA</subject><subject>Transfection</subject><issn>0021-9738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><recordid>eNpVkE9LAzEQxXNQaq0e_ABCrh5Wk93sJjl4kOKfSkVBPS-zyWx3pd0sm1Qp-OFNqRQ9DA_mvd8MPELOOLvkXKZXj9NZ1ELkB2TMWMoTLTN1RI69_2CMC5GLERlJxUWR8jH5floHCK3rPG07Ghqki-XaOI9JkfSN830DAXzcYocUhjjeO9NCQEu_2tDE-Ma46FIf3AALpLb1uCXCpkdPOVDobJTXF1qtA-1coLza7cwJOaxh6fH0Vyfk_e72bfqQzJ_vZ9ObeWKyQocEU2SmYpm1YGuNqNJKC7BVnuUCTao4S5WSUmlQObBc5pWUMmPKMC1qXulsQq53d_t1tUJrsAsDLMt-aFcwbEoHbfnf6dqmXLjPMtW54CLyFzveDM77Aes9ylm5Lb3clx6z539_7ZO_jWc_ZcSAEA</recordid><startdate>199501</startdate><enddate>199501</enddate><creator>Lei, K J</creator><creator>Shelly, L L</creator><creator>Lin, B</creator><creator>Sidbury, J B</creator><creator>Chen, Y T</creator><creator>Nordlie, R C</creator><creator>Chou, J Y</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>199501</creationdate><title>Mutations in the glucose-6-phosphatase gene are associated with glycogen storage disease types 1a and 1aSP but not 1b and 1c</title><author>Lei, K J ; Shelly, L L ; Lin, B ; Sidbury, J B ; Chen, Y T ; Nordlie, R C ; Chou, J Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c369t-e2e0cb03ddadf9ee82b94adb5354ec28102887789a85a0575b777308c094f1b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Alleles</topic><topic>Amino Acid Sequence</topic><topic>Base Sequence</topic><topic>Cells, Cultured</topic><topic>Cloning, Molecular</topic><topic>Genome, Human</topic><topic>Glucose-6-Phosphatase - genetics</topic><topic>Glycogen Storage Disease Type I - classification</topic><topic>Glycogen Storage Disease Type I - enzymology</topic><topic>Glycogen Storage Disease Type I - genetics</topic><topic>Heterozygote</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Site-Directed</topic><topic>Mutation - genetics</topic><topic>Polymerase Chain Reaction</topic><topic>Sequence Analysis, DNA</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lei, K J</creatorcontrib><creatorcontrib>Shelly, L L</creatorcontrib><creatorcontrib>Lin, B</creatorcontrib><creatorcontrib>Sidbury, J B</creatorcontrib><creatorcontrib>Chen, Y T</creatorcontrib><creatorcontrib>Nordlie, R C</creatorcontrib><creatorcontrib>Chou, J Y</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lei, K J</au><au>Shelly, L L</au><au>Lin, B</au><au>Sidbury, J B</au><au>Chen, Y T</au><au>Nordlie, R C</au><au>Chou, J Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mutations in the glucose-6-phosphatase gene are associated with glycogen storage disease types 1a and 1aSP but not 1b and 1c</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>1995-01</date><risdate>1995</risdate><volume>95</volume><issue>1</issue><spage>234</spage><epage>240</epage><pages>234-240</pages><issn>0021-9738</issn><abstract>Glycogen storage disease (GSD) type 1, which is caused by the deficiency of glucose-6-phosphatase (G6Pase), is an autosomal recessive disease with heterogenous symptoms. Two models of G6Pase catalysis have been proposed to explain the observed heterogeneities. The translocase-catalytic unit model proposes that five GSD type 1 subgroups exist which correspond to defects in the G6Pase catalytic unit (1a), a stabilizing protein (1aSP), the glucose-6-P (1b), phosphate/pyrophosphate (1c), and glucose (1d) translocases. Conversely, the conformation-substrate-transport model suggests that G6Pase is a single multifunctional membrane channel protein possessing both catalytic and substrate (or product) transport activities. We have recently demonstrated that mutations in the G6Pase catalytic unit cause GSD type 1a. To elucidate whether mutations in the G6Pase gene are responsible for other GSD type 1 subgroups, we characterized the G6Pase gene of GSD type 1b, 1c, and 1aSP patients. Our results show that the G6Pase gene of GSD type 1b and 1c patients is normal, consistent with the translocase-catalytic unit model of G6Pase catalysis. However, a mutation in exon 2 that converts an Arg at codon 83 to a Cys (R83C) was identified in both G6Pase alleles of the type 1aSP patient. The R83C mutation was also demonstrated in one homozygous and five heterogenous GSD type 1a patients, indicating that type 1aSP is a misclassification of GSD type 1a. We have also analyzed the G6Pase gene of seven additional type 1a patients and uncovered two new mutations that cause GSD type 1a.</abstract><cop>United States</cop><pmid>7814621</pmid><doi>10.1172/JCI117645</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0021-9738 |
ispartof | The Journal of clinical investigation, 1995-01, Vol.95 (1), p.234-240 |
issn | 0021-9738 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_295414 |
source | EZB Free E-Journals; PubMed Central |
subjects | Alleles Amino Acid Sequence Base Sequence Cells, Cultured Cloning, Molecular Genome, Human Glucose-6-Phosphatase - genetics Glycogen Storage Disease Type I - classification Glycogen Storage Disease Type I - enzymology Glycogen Storage Disease Type I - genetics Heterozygote Homozygote Humans Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Mutation - genetics Polymerase Chain Reaction Sequence Analysis, DNA Transfection |
title | Mutations in the glucose-6-phosphatase gene are associated with glycogen storage disease types 1a and 1aSP but not 1b and 1c |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T01%3A04%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mutations%20in%20the%20glucose-6-phosphatase%20gene%20are%20associated%20with%20glycogen%20storage%20disease%20types%201a%20and%201aSP%20but%20not%201b%20and%201c&rft.jtitle=The%20Journal%20of%20clinical%20investigation&rft.au=Lei,%20K%20J&rft.date=1995-01&rft.volume=95&rft.issue=1&rft.spage=234&rft.epage=240&rft.pages=234-240&rft.issn=0021-9738&rft_id=info:doi/10.1172/JCI117645&rft_dat=%3Cpubmed_cross%3E7814621%3C/pubmed_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c369t-e2e0cb03ddadf9ee82b94adb5354ec28102887789a85a0575b777308c094f1b93%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/7814621&rfr_iscdi=true |