Quaternary diagnostics scheme for mucolipidosis II and detection of novel mutation in GNPTAB gene
Abstract Background Mucolipidosis II (ML II α/β) is an inherited lysosomal storage disorder caused by deficiency of GlcNAc-phosphotransferase enzyme and results in mis-targeting of multiple lysosomal enzymes. Affected patients are characterized by skeletal deformities and developmental delay. Homozy...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-08-01
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| Series: | Journal of Genetic Engineering and Biotechnology |
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| Online Access: | https://doi.org/10.1186/s43141-021-00204-4 |
| _version_ | 1797203703716904960 |
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| author | Mona L. Essawi Ekram M. Fateen Hanan A. Atia Noura R. Eissa Eman H. Aboul-Ezz Mona M. Ibrahim Heba A. Hassan Samia A. Temtamy |
| author_facet | Mona L. Essawi Ekram M. Fateen Hanan A. Atia Noura R. Eissa Eman H. Aboul-Ezz Mona M. Ibrahim Heba A. Hassan Samia A. Temtamy |
| author_sort | Mona L. Essawi |
| collection | DOAJ |
| description | Abstract Background Mucolipidosis II (ML II α/β) is an inherited lysosomal storage disorder caused by deficiency of GlcNAc-phosphotransferase enzyme and results in mis-targeting of multiple lysosomal enzymes. Affected patients are characterized by skeletal deformities and developmental delay. Homozygous or compound heterozygous mutations in GNPTAB gene are associated with the clinical presentation. This is the first study to characterize the underlying genetics of ML among a cohort of Egyptian patients. ML II diagnosis established by clinical assessment, biochemical evaluation of enzymes, electron microscopy examination of gingival inclusion bodies, and molecular study of GNPTAB gene using targeted next-generation sequencing panel in 8 patients form 8 unrelated Egyptian families. Results Sequencing revealed 3 mutations in GNPTAB gene; 1 novel frame-shift mutation in exon 19 (c.3488_3488delC) and 2 previously reported mutations (c.1759C>T in exon 13 and c.3503_3504delTC in exon 19). All patients were homozygous for their corresponding mutations and the parents were consanguineous. Conclusions According to the established quaternary diagnostic scheme, ML II was the final diagnosis in eight patients. The most common mutation was the frame shift c.3503_3504delTC mutation, found in 5 patients and associated with a severe phenotype. |
| first_indexed | 2024-04-24T08:23:33Z |
| format | Article |
| id | doaj.art-61c613f793f842c38196da2d5c2520e0 |
| institution | Directory Open Access Journal |
| issn | 2090-5920 |
| language | English |
| last_indexed | 2024-04-24T08:23:33Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Genetic Engineering and Biotechnology |
| spelling | doaj.art-61c613f793f842c38196da2d5c2520e02024-04-16T23:53:47ZengElsevierJournal of Genetic Engineering and Biotechnology2090-59202021-08-0119111010.1186/s43141-021-00204-4Quaternary diagnostics scheme for mucolipidosis II and detection of novel mutation in GNPTAB geneMona L. Essawi0Ekram M. Fateen1Hanan A. Atia2Noura R. Eissa3Eman H. Aboul-Ezz4Mona M. Ibrahim5Heba A. Hassan6Samia A. Temtamy7Department of Medical Molecular Genetics, Division of Human Genetics and Genome ResearchDepartment of Medical Molecular Genetics, Division of Human Genetics and Genome ResearchDepartment of Pharmacology and Toxicology, College of Pharmacy, Hail UniversityDepartment of Medical Molecular Genetics, Division of Human Genetics and Genome ResearchNational Research CentreNational Research CentreDepartment of Medical Molecular Genetics, Division of Human Genetics and Genome ResearchNational Research CentreAbstract Background Mucolipidosis II (ML II α/β) is an inherited lysosomal storage disorder caused by deficiency of GlcNAc-phosphotransferase enzyme and results in mis-targeting of multiple lysosomal enzymes. Affected patients are characterized by skeletal deformities and developmental delay. Homozygous or compound heterozygous mutations in GNPTAB gene are associated with the clinical presentation. This is the first study to characterize the underlying genetics of ML among a cohort of Egyptian patients. ML II diagnosis established by clinical assessment, biochemical evaluation of enzymes, electron microscopy examination of gingival inclusion bodies, and molecular study of GNPTAB gene using targeted next-generation sequencing panel in 8 patients form 8 unrelated Egyptian families. Results Sequencing revealed 3 mutations in GNPTAB gene; 1 novel frame-shift mutation in exon 19 (c.3488_3488delC) and 2 previously reported mutations (c.1759C>T in exon 13 and c.3503_3504delTC in exon 19). All patients were homozygous for their corresponding mutations and the parents were consanguineous. Conclusions According to the established quaternary diagnostic scheme, ML II was the final diagnosis in eight patients. The most common mutation was the frame shift c.3503_3504delTC mutation, found in 5 patients and associated with a severe phenotype.https://doi.org/10.1186/s43141-021-00204-4MucolipidosisGNPTAB geneNGSML IIEgyptianMutations |
| spellingShingle | Mona L. Essawi Ekram M. Fateen Hanan A. Atia Noura R. Eissa Eman H. Aboul-Ezz Mona M. Ibrahim Heba A. Hassan Samia A. Temtamy Quaternary diagnostics scheme for mucolipidosis II and detection of novel mutation in GNPTAB gene Journal of Genetic Engineering and Biotechnology Mucolipidosis GNPTAB gene NGS ML II Egyptian Mutations |
| title | Quaternary diagnostics scheme for mucolipidosis II and detection of novel mutation in GNPTAB gene |
| title_full | Quaternary diagnostics scheme for mucolipidosis II and detection of novel mutation in GNPTAB gene |
| title_fullStr | Quaternary diagnostics scheme for mucolipidosis II and detection of novel mutation in GNPTAB gene |
| title_full_unstemmed | Quaternary diagnostics scheme for mucolipidosis II and detection of novel mutation in GNPTAB gene |
| title_short | Quaternary diagnostics scheme for mucolipidosis II and detection of novel mutation in GNPTAB gene |
| title_sort | quaternary diagnostics scheme for mucolipidosis ii and detection of novel mutation in gnptab gene |
| topic | Mucolipidosis GNPTAB gene NGS ML II Egyptian Mutations |
| url | https://doi.org/10.1186/s43141-021-00204-4 |
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