Fanconi-Bickel syndrome versus osteogenesis imperfeeta: An Iranian case with a novel mutation in glucose transporter 2 gene, and review of literature

Hadipour, Fatemeh; Sarkheil, Peymaneh; Noruzinia, Mehrdad; Hadipour, Zahra; Baghdadi, Taghi; Shafeghati, Yousef

doi:10.4103/0971-6866.112906

Cited by 6 publications

(1 citation statement)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hypophosphatemia is a common feature of many other diseases which are not considered to be a classical form of HR. Fanconi–Bickel syndrome, FBS (MIM # 227810) an autosomal recessive disease is one such entity that mimics hypophosphatemic rickets as well as osteogenesis imperfecta (OI) [ 27 ]. FBS is caused due to biallelic variants in SLC2A2 (solute carrier family 2 member 2) or GLUT2 (glucose transporter 2 protein) known to mediate bidirectional glucose transport [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Exome Sequencing in Monogenic Forms of Rickets

et al. 2023

View full text Add to dashboard Cite

Objective To understand the phenotypic and genotypic spectrum of genetic forms of rickets in 10 families. Methods Detailed clinical, radiographic, and biochemical evaluation of 10 families with phenotypes suggestive of a genetic cause of rickets was performed. Molecular testing using exome sequencing aided in the diagnosis of six different forms of known genetic causes. Results Eleven disease-causing variants including five previously reported variants (CYP27B1:c.1319_1325dup, p.(Phe443Profs*24), VDR:c.1171C>T, p.(Arg391Cys), PHEX: c.1586_1586+1del, PHEX: c.1482+5G>C, PHEX: c.58C>T, p.(Arg20*)) and six novel variants (CYP27B1:c.974C>T, p.(Thr325Met), CYP27B1: c.1376G>A, p.(Arg459His), CYP2R1: c.595C>T, p.(Arg199*), CYP2R1:c.1330G>C, p.(Gly444Arg),SLC34A3:c.1336-11_1336-1del, SLC2A2: c.589G>C, p.(Val197Leu)) in the genes known to cause monogenic rickets were identified. Conclusion The authors hereby report a case series of individuals from India with a molecular diagnosis of rickets and provide the literature review which would help in enhancing the clinical and molecular profile for rapid and differential diagnosis of rickets.

show abstract

Section: Discussionmentioning

confidence: 99%

Exome Sequencing in Monogenic Forms of Rickets

et al. 2023

View full text Add to dashboard Cite

show abstract

Functional and structural analysis of rareSLC2A2variants associated with Fanconi‐Bickel syndrome and metabolic traits

et al. 2019

View full text Add to dashboard Cite

Deleterious variants in SLC2A2 cause Fanconi‐Bickel Syndrome (FBS), a glycogen storage disorder, whereas less common variants in SLC2A2 associate with numerous metabolic diseases. Phenotypic heterogeneity in FBS has been observed, but its causes remain unknown. Our goal was to functionally characterize rare SLC2A2 variants found in FBS and metabolic disease‐associated variants to understand the impact of these variants on GLUT2 activity and expression and establish genotype‐phenotype correlations. Complementary RNA‐injected Xenopus laevis oocytes were used to study mutant transporter activity and membrane expression. GLUT2 homology models were constructed for mutation analysis using GLUT1, GLUT3, and XylE as templates. Seventeen FBS variants were characterized. Only c.457_462delCTTATA (p.Leu153_Ile154del) exhibited residual glucose uptake. Functional characterization revealed that only half of the variants were expressed on the plasma membrane. Most less common variants (except c.593 C>A (p.Thr198Lys) and c.1087 G>T (p.Ala363Ser)) exhibited similar GLUT2 transport activity as the wild type. Structural analysis of GLUT2 revealed that variants affect substrate‐binding, steric hindrance, or overall transporter structure. The mutant transporter that is associated with a milder FBS phenotype, p.Leu153_Ile154del, retained transport activity. These results improve our overall understanding of the underlying causes of FBS and impact of GLUT2 function on various clinical phenotypes ranging from rare to common disease.

show abstract

Molecular spectrum and differential diagnosis in patients referred with sporadic or autosomal recessive osteogenesis imperfecta

Caparrós-Martín

Aglan

Temtamy

et al. 2016

Molec Gen & Gen Med

View full text Add to dashboard Cite

BackgroundOsteogenesis imperfecta (OI) is a heterogeneous bone disorder characterized by recurrent fractures. Although most cases of OI have heterozygous mutations in COL1A1 or COL1A2 and show autosomal dominant inheritance, during the last years there has been an explosion in the number of genes responsible for both recessive and dominant forms of this condition. Herein, we have analyzed a cohort of patients with OI, all offspring of unaffected parents, to determine the spectrum of variants accounting for these cases. Twenty patients had nonrelated parents and were sporadic, and 21 were born to consanguineous relationships.MethodsMutation analysis was performed using a next‐generation sequencing gene panel, homozygosity mapping, and whole exome sequencing (WES).ResultsPatients offspring of nonconsanguineous parents were mostly identified with COL1A1 or COL1A2 heterozygous changes, although there were also a few cases with IFITM5 and WNT1 heterozygous mutations. Only one sporadic patient was a compound heterozygote for two recessive mutations. Patients offspring of consanguineous parents showed homozygous changes in a variety of genes including CRTAP,FKBP10,LEPRE1,PLOD2,PPIB,SERPINF1,TMEM38B, and WNT1. In addition, two patients born to consanguineous parents were found to have de novo COL1A1 heterozygous mutations demonstrating that causative variants in the collagen I structural genes cannot be overlooked in affected children from consanguineous couples. Further to this, WES analysis in probands lacking mutations in OI genes revealed deleterious variants in SCN9A,NTRK1, and SLC2A2, which are associated with congenital indifference to pain (CIP) and Fanconi–Bickel syndrome (FBS).ConclusionThis work provides useful information for clinical and genetic diagnosis of OI patients with no positive family history of this disease. Our data also indicate that CIP and FBS are conditions to be considered in the differential diagnosis of OI and suggest a positive role of SCN9A and NTRK1 in bone development.

show abstract

Fanconi-Bickel syndrome versus osteogenesis imperfeeta: An Iranian case with a novel mutation in glucose transporter 2 gene, and review of literature

Cited by 6 publications

References 11 publications

Exome Sequencing in Monogenic Forms of Rickets

Exome Sequencing in Monogenic Forms of Rickets

Functional and structural analysis of rareSLC2A2variants associated with Fanconi‐Bickel syndrome and metabolic traits

Molecular spectrum and differential diagnosis in patients referred with sporadic or autosomal recessive osteogenesis imperfecta

Contact Info

Product

Resources

About