{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:48:12Z","timestamp":1787662092873,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010591","name":"Tiroler Wissenschaftsfonds","doi-asserted-by":"publisher","award":["UNI-0404\/2386"],"award-info":[{"award-number":["UNI-0404\/2386"]}],"id":[{"id":"10.13039\/501100010591","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Congenital glucose-galactose malabsorption is a rare autosomal recessive disorder caused by mutations in SLC5A1 encoding the apical sodium\/glucose cotransporter SGLT1. We present clinical and molecular data from eleven affected individuals with congenital glucose-galactose malabsorption from four unrelated, consanguineous Turkish families. Early recognition and timely management by eliminating glucose and galactose from the diet are fundamental for affected individuals to survive and develop normally. We identified novel SLC5A1 missense variants, p.Gly43Arg and p.Ala92Val, which were linked to disease in two families. Stable expression in CaCo-2 cells showed that the p.Ala92Val variant did not reach the plasma membrane, but was retained in the endoplasmic reticulum. The p.Gly43Arg variant, however, displayed processing and plasma membrane localization comparable to wild-type SGLT1. Glycine-43 displays nearly invariant conservation in the relevant structural family of cotransporters and exchangers, and localizes to SGLT1 transmembrane domain TM0. p.Gly43Arg represents the first disease-associated variant in TM0; however, the role of TM0 in the SGLT1 function has not been established. In summary, we are expanding the mutational spectrum of this rare disorder.<\/jats:p>","DOI":"10.3390\/genes14071359","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:25:21Z","timestamp":1687911921000},"page":"1359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["SLC5A1 Variants in Turkish Patients with Congenital Glucose-Galactose Malabsorption"],"prefix":"10.3390","volume":"14","author":[{"given":"Ferda \u00d6.","family":"Ho\u015fnut","sequence":"first","affiliation":[{"name":"Department of Pediatric Gastroenterology, Hepatology and Nutrition, Dr. Sami Ulus Maternity and Child Health and Diseases Training and Research Hospital, University of Health Sciences, 06080 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7155-0315","authenticated-orcid":false,"given":"Andreas R.","family":"Janecke","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Medical University of Innsbruck, 6020 Innsbruck, Austria"},{"name":"Institute of Human Genetics, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fclseren","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Hepatology and Nutrition, Dr. Sami Ulus Maternity and Child Health and Diseases Training and Research Hospital, University of Health Sciences, 06080 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2515-4490","authenticated-orcid":false,"given":"Georg F.","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Medical University of Innsbruck, 6020 Innsbruck, Austria"},{"name":"Institute of Cell Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7683-371X","authenticated-orcid":false,"given":"Naz G.","family":"Lafc\u0131","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Hacettepe University Faculty of Medicine, 06230 Ankara, Turkey"},{"name":"Department of Medical Genetics, Dr. Sami Ulus Maternity and Child Health and Diseases Training and Research Hospital, University of Health Sciences, 06080 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Bichler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Medical University of Innsbruck, 6020 Innsbruck, Austria"},{"name":"Institute of Cell Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8908-5589","authenticated-orcid":false,"given":"Thomas","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1116-2120","authenticated-orcid":false,"given":"Lukas A.","family":"Huber","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1205-2225","authenticated-orcid":false,"given":"Taras","family":"Valovka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Medical University of Innsbruck, 6020 Innsbruck, Austria"},{"name":"Institute of Cell Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysel \u00dc.","family":"Aksu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Hepatology and Nutrition, Ankara Bilkent Hospital, University of Health Sciences, 06800 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1152\/physrev.00055.2009","article-title":"Biology of human sodium glucose transporters","volume":"91","author":"Wright","year":"2011","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1111\/jpc.14702","article-title":"Literature review on congenital glucose\u2013galactose malabsorption from 2001 to 2019","volume":"56","author":"Wang","year":"2020","journal-title":"J. Paediatr. Child Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1097\/00005176-199612000-00008","article-title":"Congenital glucose-galactose malabsorption in Arab children","volume":"23","author":"Abdullah","year":"1996","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/350354a0","article-title":"Glucose\/galactose malabsorption caused by a defect in the Na+\/glucose cotransporter","volume":"350","author":"Turk","year":"1991","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"zqab040","DOI":"10.1093\/function\/zqab040","article-title":"The Molecular Basis of Glucose Galactose Malabsorption in a Large Swedish Pedigree","volume":"2","author":"Lostao","year":"2021","journal-title":"Function"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/s41586-021-04211-w","article-title":"Structure and mechanism of the SGLT family of glucose transporters","volume":"601","author":"Han","year":"2022","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1097\/MPG.0000000000001694","article-title":"SLC5A1 Mutations in Saudi Arabian Patients with Congenital Glucose-Galactose Malabsorption","volume":"66","author":"ALSaleem","year":"2018","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.1007\/s10620-020-06792-4","article-title":"Long-Term Dietary Changes in Subjects with Glucose Galactose Malabsorption Secondary to Biallelic Mutations of SLC5A1","volume":"66","author":"Chan","year":"2021","journal-title":"Dig. Dis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ajg.2014.01.004","article-title":"Congenital glucose\u2013galactose malabsorption: A descriptive study of clinical characteristics and outcome from Western Saudi Arabia","volume":"15","author":"Saadah","year":"2014","journal-title":"Arab J. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s10620-016-4348-2","article-title":"Congenital Glucose\u2013Galactose Malabsorption in a Turkish Newborn: A Novel Mutation of Na+\/Glucose Cotransporter Gene","volume":"62","author":"Atay","year":"2017","journal-title":"Dig. Dis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9873","DOI":"10.1128\/JVI.72.12.9873-9880.1998","article-title":"Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery","volume":"72","author":"Zufferey","year":"1998","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Leitner, P.D., Jakschitz, T., Gstir, R., Stuppner, S., Perkams, S., Kruus, M., Trockenbacher, A., Griesbeck, C., Bonn, G.K., and Huber, L.A. (2022). Anti-Inflammatory Extract from Soil Algae Chromochloris zofingiensis Targeting TNFR\/NF-\u03baB Signaling at Different Levels. Cells, 11.","DOI":"10.3390\/cells11091407"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"W350","DOI":"10.1093\/nar\/gky300","article-title":"DynaMut: Predicting the impact of mutations on protein conformation, flexibility and stability","volume":"46","author":"Rodrigues","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.jmb.2016.12.004","article-title":"Arpeggio: A Web Server for Calculating and Visualising Interatomic Interactions in Protein Structures","volume":"429","author":"Jubb","year":"2017","journal-title":"J. Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Frappier, V., and Najmanovich, R.J. (2014). A coarse-grained elastic network atom contact model and its use in the simulation of protein dynamics and the prediction of the effect of mutations. PLoS Comput. Biol., 10.","DOI":"10.1371\/journal.pcbi.1003569"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1055\/s-0040-1719161","article-title":"A Case of Congenital Glucose Galactose Malabsorption with a New Mutation in the SLC5A1 Gene","volume":"11","author":"Akduman","year":"2022","journal-title":"J. Pediatr. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1007\/s00431-008-0681-6","article-title":"Nephrocalcinosis in glucose-galactose malabsorption: Nephrocalcinosis and proximal tubular dysfunction in a young infant with a novel mutation of SGLT1","volume":"167","author":"Soylu","year":"2008","journal-title":"Eur. J. Pediatr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"C737","DOI":"10.1152\/ajpcell.00041.2003","article-title":"More than apical: Distribution of SGLT1 in Caco-2 cells","volume":"285","author":"Kipp","year":"2003","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s00439-022-02501-5","article-title":"The genetics of monogenic intestinal epithelial disorders","volume":"142","author":"Babcock","year":"2022","journal-title":"Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.bpg.2016.03.004","article-title":"Congenital intestinal diarrhoeal diseases: A diagnostic and therapeutic challenge","volume":"30","author":"Posovszky","year":"2016","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/S0022-3476(71)80357-8","article-title":"Glucose-galactose malabsorption in an Oriental-Iraqui Jewish family","volume":"78","author":"Lebenthal","year":"1971","journal-title":"J. Pediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/j.1399-0004.2010.01440.x","article-title":"Multiple sequence variations in SLC5A1 gene are associated with glucose-galactose malabsorption in a large cohort of Old Order Amish","volume":"79","author":"Xin","year":"2011","journal-title":"Clin. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0925-4439(98)00109-4","article-title":"Missense mutations in SGLT1 cause glucose\u2013galactose malabsorption by trafficking defects","volume":"1453","author":"Lam","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1267\/ahc.06024","article-title":"Apical localization of sodium-dependent glucose transporter SGLT1 is maintained by cholesterol and microtubules","volume":"39","author":"Suzuki","year":"2006","journal-title":"Acta Histochem. Cytochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e13062","DOI":"10.14814\/phy2.13062","article-title":"Real-time imaging of sodium glucose transporter (SGLT1) trafficking and activity in single cells","volume":"5","author":"Ghezzi","year":"2017","journal-title":"Physiol. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1091\/mbc.e05-02-0100","article-title":"Cholesterol is required for efficient endoplasmic reticulum-to-Golgi transport of secretory membrane proteins","volume":"17","author":"Ridsdale","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"ref_27","first-page":"e18440","article-title":"Congenital Glucose-Galactose Malabsorption: A Case with a Novel SLC5A1 Mutation in a Saudi Infant","volume":"13","author":"Alamoudi","year":"2021","journal-title":"Cureus"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/7\/1359\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:02:11Z","timestamp":1760126531000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/7\/1359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,27]]},"references-count":27,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["genes14071359"],"URL":"https:\/\/doi.org\/10.3390\/genes14071359","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,27]]}}}