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

Genes

Sarah C. Grünert¹  Anke Schumann¹  Ute Spiekerkoetter¹  Konstantinos Tsiakas²  René Santer²  Simona Murko²  Federico Baronio³ 

[1] Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center—University of Freiburg, 79106 Freiburg, Germany;Department of Pediatrics, University Medical Center Eppendorf, 20246 Hamburg, Germany;Pediatric Unit, Department of Medical and Surgical Sciences, Regional Center for Expanded Newborn Screening, S. Orsola—Malpighi University Hospital, 40138 Bologna, Italy;

关键词: Fanconi-Bickel syndrome;    genotype-phenotype correlation;    GLUT2;    SLC2A2;    glycogen storage disease;    glucosuria;   

DOI  :  10.3390/genes12111785

来源: DOAJ

【 摘 要 】

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 GLUT2 (SLC2A2) 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 Xenopus oocytes. GLUT2 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 GLUT2 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 GLUT2 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.

【 授权许可】

Unknown