{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:07:42Z","timestamp":1788584862509,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,12,5]],"date-time":"2020-12-05T00:00:00Z","timestamp":1607126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81471897"],"award-info":[{"award-number":["81471897"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81701621"],"award-info":[{"award-number":["81701621"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771766"],"award-info":[{"award-number":["81771766"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Glycogen storage disease (GSD) type Ib is an autosomal recessive disease caused by defects of glucose\u20106\u2010phosphate transporter (G6PT), encoded by the <jats:italic>SLC37A4<\/jats:italic> gene. To date, over 100 mutations have been revealed in the <jats:italic>SLC37A4<\/jats:italic> gene. GSD\u2010Ib patients manifest a metabolic phenotype of impaired blood glucose homeostasis and also carry the additional complications of neutropenia and myeloid dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we present two daughters with an initial diagnosis of gout in a Chinese consanguineous family. Whole\u2010exome sequencing was performed to identify the mutations. The mechanism of leukocytopenia was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Whole\u2010exome sequencing analysis of the proband identified a novel homozygous p.P119L mutation in <jats:italic>SLC37A4<\/jats:italic>, leading to a diagnosis of GSD\u2010Ib. We found that the potential pathogenic p.P119L mutation leads to an unusual phenotype characterized by gout at onset, and GSD\u2010Ib arising from this variant also manifests multiple metabolic abnormalities, leukocytopenia, and anemia, but no hepatomegaly. The leukocytes from the proband showed increased mRNA levels of sXBP\u20101, BIP, and CHOP genes in the unfolded protein response pathway, and enhanced Bax mRNA and caspase\u20103 activity, which might contribute to leukocytopenia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings broaden the variation spectrum of <jats:italic>SLC37A4<\/jats:italic> and suggest no strict genotype\u2013phenotype correlations in GSD\u2010Ib patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1568","type":"journal-article","created":{"date-parts":[[2020,12,6]],"date-time":"2020-12-06T07:14:21Z","timestamp":1607238861000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A novel <i>SLC37A4<\/i> missense mutation in GSD\u2010Ib without hepatomegaly causes enhanced leukocytes endoplasmic reticulum stress and apoptosis"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2134-4243","authenticated-orcid":false,"given":"Qianyun","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Rheumatology Xiangya Hospital Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics The Second Xiangya Hospital Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Xiangya Hospital Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Xiangya Hospital Central South University Changsha 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