Evidence for a Genotype–Phenotype Correlation in Patients with Pathogenic <i>GLUT2</i> (<i>SLC2A2</i>) Variants

Fanconi-Bickel syndrome (FBS) is a very rare but distinct clinical entity with the combined features of hepatic glycogen storage disease, generalized proximal renal tubular dysfunction with disproportionately severe glucosuria, and impaired galactose tolerance. Here, we report five cases (out of 93...

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Autores principales:	Sarah C. Grünert, Anke Schumann, Federico Baronio, Konstantinos Tsiakas, Simona Murko, Ute Spiekerkoetter, René Santer
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Fanconi-Bickel syndrome genotype-phenotype correlation <i>GLUT2</i> <i>SLC2A2</i> glycogen storage disease glucosuria Genetics QH426-470
Acceso en línea:	https://doaj.org/article/c51b0165426a4ce1bd7209aa1a9f89b4
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spelling	oai:doaj.org-article:c51b0165426a4ce1bd7209aa1a9f89b42021-11-25T17:41:56ZEvidence for a Genotype–Phenotype Correlation in Patients with Pathogenic <i>GLUT2</i> (<i>SLC2A2</i>) Variants10.3390/genes121117852073-4425https://doaj.org/article/c51b0165426a4ce1bd7209aa1a9f89b42021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1785https://doaj.org/toc/2073-4425Fanconi-Bickel syndrome (FBS) is a very rare but distinct clinical entity with the combined features of hepatic glycogen storage disease, generalized proximal renal tubular dysfunction with disproportionately severe glucosuria, and impaired galactose tolerance. Here, we report five cases (out of 93 diagnosed in our lab) with pathogenic variants on both <i>GLUT2</i> (<i>SLC2A2</i>) alleles. They come from 3 families and presented with an exceptionally mild clinical course. This course was correlated to data from old and most recent expression and transport studies in <i>Xenopus</i> oocytes. <i>GLUT2</i> genotype in patients 1 and 2 was p.[153_4delLI];[P417R] with the first variant exhibiting normal membrane expression and partially retained transport activity (5.8%) for 2-deoxyglucose. In patient 3, the very first <i>GLUT2</i> variant ever detected (p.V197I) was found, but for the first time it was present in a patient in the homozygous state. This variant had also shown unaffected membrane expression and remarkable residual activity (8%). The genotype in patient 4, p.[153_4delLI];[(E440A)], again included the 2-amino-acid deletion with residual transporter function, and patient 5 is the first found to be homozygous for this variant. Our results provide further evidence for a genotype-phenotype correlation in patients with <i>GLUT2</i> variants; non-functional variants result in the full picture of FBS while dysfunctional variants may result in milder presentations, even glucosuria only, without other typical signs of FBS.Sarah C. GrünertAnke SchumannFederico BaronioKonstantinos TsiakasSimona MurkoUte SpiekerkoetterRené SanterMDPI AGarticleFanconi-Bickel syndromegenotype-phenotype correlation<i>GLUT2</i><i>SLC2A2</i>glycogen storage diseaseglucosuriaGeneticsQH426-470ENGenes, Vol 12, Iss 1785, p 1785 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Fanconi-Bickel syndrome genotype-phenotype correlation <i>GLUT2</i> <i>SLC2A2</i> glycogen storage disease glucosuria Genetics QH426-470
spellingShingle	Fanconi-Bickel syndrome genotype-phenotype correlation <i>GLUT2</i> <i>SLC2A2</i> glycogen storage disease glucosuria Genetics QH426-470 Sarah C. Grünert Anke Schumann Federico Baronio Konstantinos Tsiakas Simona Murko Ute Spiekerkoetter René Santer Evidence for a Genotype–Phenotype Correlation in Patients with Pathogenic <i>GLUT2</i> (<i>SLC2A2</i>) Variants
description	Fanconi-Bickel syndrome (FBS) is a very rare but distinct clinical entity with the combined features of hepatic glycogen storage disease, generalized proximal renal tubular dysfunction with disproportionately severe glucosuria, and impaired galactose tolerance. Here, we report five cases (out of 93 diagnosed in our lab) with pathogenic variants on both <i>GLUT2</i> (<i>SLC2A2</i>) alleles. They come from 3 families and presented with an exceptionally mild clinical course. This course was correlated to data from old and most recent expression and transport studies in <i>Xenopus</i> oocytes. <i>GLUT2</i> genotype in patients 1 and 2 was p.[153_4delLI];[P417R] with the first variant exhibiting normal membrane expression and partially retained transport activity (5.8%) for 2-deoxyglucose. In patient 3, the very first <i>GLUT2</i> variant ever detected (p.V197I) was found, but for the first time it was present in a patient in the homozygous state. This variant had also shown unaffected membrane expression and remarkable residual activity (8%). The genotype in patient 4, p.[153_4delLI];[(E440A)], again included the 2-amino-acid deletion with residual transporter function, and patient 5 is the first found to be homozygous for this variant. Our results provide further evidence for a genotype-phenotype correlation in patients with <i>GLUT2</i> variants; non-functional variants result in the full picture of FBS while dysfunctional variants may result in milder presentations, even glucosuria only, without other typical signs of FBS.
format	article
author	Sarah C. Grünert Anke Schumann Federico Baronio Konstantinos Tsiakas Simona Murko Ute Spiekerkoetter René Santer
author_facet	Sarah C. Grünert Anke Schumann Federico Baronio Konstantinos Tsiakas Simona Murko Ute Spiekerkoetter René Santer
author_sort	Sarah C. Grünert
title	Evidence for a Genotype–Phenotype Correlation in Patients with Pathogenic <i>GLUT2</i> (<i>SLC2A2</i>) Variants
title_short	Evidence for a Genotype–Phenotype Correlation in Patients with Pathogenic <i>GLUT2</i> (<i>SLC2A2</i>) Variants
title_full	Evidence for a Genotype–Phenotype Correlation in Patients with Pathogenic <i>GLUT2</i> (<i>SLC2A2</i>) Variants
title_fullStr	Evidence for a Genotype–Phenotype Correlation in Patients with Pathogenic <i>GLUT2</i> (<i>SLC2A2</i>) Variants
title_full_unstemmed	Evidence for a Genotype–Phenotype Correlation in Patients with Pathogenic <i>GLUT2</i> (<i>SLC2A2</i>) Variants
title_sort	evidence for a genotype–phenotype correlation in patients with pathogenic <i>glut2</i> (<i>slc2a2</i>) variants
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c51b0165426a4ce1bd7209aa1a9f89b4
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Evidence for a Genotype–Phenotype Correlation in Patients with Pathogenic <i>GLUT2</i> (<i>SLC2A2</i>) Variants

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