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Genotype-Phenotype Correlation and Description of Two Novel Mutations in Iranian Patients With Glycogen Storage Disease 1B (Gsd1b) Publisher Pubmed



Eghbali M1 ; Abiri M2 ; Talebi S2 ; Noroozi Z3 ; Shakiba M4 ; Rostami P5 ; Alimadadi H6 ; Najafi M6 ; Yazarlou F1 ; Rabbani A5 ; Modarressi MH1
Authors
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Authors Affiliations
  1. 1. Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pediatric Endocrinology and Metabolism, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Growth and Development Research Center, Department of Endocrinology, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Gastroenterology, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran

Source: Orphanet Journal of Rare Diseases Published:2020


Abstract

Background: Glycogen storage disease (GSD) is a rare inborn error of the synthesis or degradation of glycogen metabolism. GSD1, the most common type of GSD, is categorized into GSD1a and GSD1b which caused by the deficiency of glucose-6-phosphatase (G6PC) and glucose-6-phosphate transporter (SLC37A4), respectively. The high rates of consanguineous marriages in Iran provide a desirable context to facilitate finding the homozygous pathogenic mutations. This study designates to evaluate the clinical and genetic characteristics of patients with GSD1b to assess the possible genotype-phenotype correlation. Results: Autozygosity mapping was performed on nineteen GSD suspected families to suggest the causative loci. The mapping was done using two panels of short tandem repeat (STR) markers linked to the corresponding genes. The patients with autozygous haplotype block for the markers flanking the genes were selected for direct sequencing. Six patients showed autozygosity in the candidate markers for SLC37A4. Three causative variants were detected. The recurrent mutation of c.1042_1043delCT (p.Leu348Valfs*53) and a novel missense mutation of c.365G > A (p.G122E) in the homozygous state were identified in the SLC37A4. In silico analysis was performed to predict the pathogenicity of the variants. A novel whole SLC37A4 gene deletion using long-range PCR and sequencing was confirmed as well. Severe and moderate neutropenia was observed in patients with frameshift and missense variants, respectively. The sibling with the whole gene deletion has shown both severe neutropenia and leukopenia. Conclusions: The results showed that the hematological findings may have an appropriate correlation with the genotype findings. However, for a definite genotype-phenotype correlation, specifically for the clinical and biochemical phenotype, further studies with larger sample sizes are needed. © 2020 The Author(s).
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