Genotype-phenotype correlation and description of two novel mutations in Iranian patients with glycogen storage disease 1b (GSD1b)
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-01-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-019-1266-3 |
| _version_ | 1818877790335795200 |
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| author | Maryam Eghbali Maryam Abiri Saeed Talebi Zahra Noroozi Marjan Shakiba Parastoo Rostami Hosein Alimadadi Mehri Najafi Fatemeh Yazarlou Ali Rabbani Mohammad Hossein Modarressi |
| author_facet | Maryam Eghbali Maryam Abiri Saeed Talebi Zahra Noroozi Marjan Shakiba Parastoo Rostami Hosein Alimadadi Mehri Najafi Fatemeh Yazarlou Ali Rabbani Mohammad Hossein Modarressi |
| author_sort | Maryam Eghbali |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T14:03:53Z |
| format | Article |
| id | doaj.art-c110bca804f849a2a1b586e83681d2f8 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-19T14:03:53Z |
| publishDate | 2020-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-c110bca804f849a2a1b586e83681d2f82022-12-21T20:18:23ZengBMCOrphanet Journal of Rare Diseases1750-11722020-01-0115111110.1186/s13023-019-1266-3Genotype-phenotype correlation and description of two novel mutations in Iranian patients with glycogen storage disease 1b (GSD1b)Maryam Eghbali0Maryam Abiri1Saeed Talebi2Zahra Noroozi3Marjan Shakiba4Parastoo Rostami5Hosein Alimadadi6Mehri Najafi7Fatemeh Yazarlou8Ali Rabbani9Mohammad Hossein Modarressi10Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical SciencesDepartment of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical SciencesDepartment of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical SciencesDepartment of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical SciencesDepartment of Pediatric Endocrinology and Metabolism, Mofid Children’s Hospital, Shahid Beheshti University of medical sciencesGrowth and Development Research Center, Department of Endocrinology, Children’s Medical Center, Tehran University of Medical SciencesDepartment of Gastroenterology, Children’s Medical Center, Tehran University of Medical ScienceDepartment of Gastroenterology, Children’s Medical Center, Tehran University of Medical ScienceDepartment of Medical Genetics, Faculty of Medicine, Tehran University of Medical SciencesGrowth and Development Research Center, Department of Endocrinology, Children’s Medical Center, Tehran University of Medical SciencesDepartment of Medical Genetics, Faculty of Medicine, Tehran University of Medical SciencesAbstract 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.https://doi.org/10.1186/s13023-019-1266-3GSD1bAutozygosity mappingNovel variantsGenotype-phenotype correlation |
| spellingShingle | Maryam Eghbali Maryam Abiri Saeed Talebi Zahra Noroozi Marjan Shakiba Parastoo Rostami Hosein Alimadadi Mehri Najafi Fatemeh Yazarlou Ali Rabbani Mohammad Hossein Modarressi Genotype-phenotype correlation and description of two novel mutations in Iranian patients with glycogen storage disease 1b (GSD1b) Orphanet Journal of Rare Diseases GSD1b Autozygosity mapping Novel variants Genotype-phenotype correlation |
| title | Genotype-phenotype correlation and description of two novel mutations in Iranian patients with glycogen storage disease 1b (GSD1b) |
| title_full | Genotype-phenotype correlation and description of two novel mutations in Iranian patients with glycogen storage disease 1b (GSD1b) |
| title_fullStr | Genotype-phenotype correlation and description of two novel mutations in Iranian patients with glycogen storage disease 1b (GSD1b) |
| title_full_unstemmed | Genotype-phenotype correlation and description of two novel mutations in Iranian patients with glycogen storage disease 1b (GSD1b) |
| title_short | Genotype-phenotype correlation and description of two novel mutations in Iranian patients with glycogen storage disease 1b (GSD1b) |
| title_sort | genotype phenotype correlation and description of two novel mutations in iranian patients with glycogen storage disease 1b gsd1b |
| topic | GSD1b Autozygosity mapping Novel variants Genotype-phenotype correlation |
| url | https://doi.org/10.1186/s13023-019-1266-3 |
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