Quaternary diagnostics scheme for mucolipidosis II and detection of novel mutation in GNPTAB gene

Background Mucolipidosis II (ML II [alpha]/[beta]) 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. Homo...

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Bibliographic Details
Published in:Journal of Genetic Engineering and Biotechnology 2021-08, Vol.19 (1), p.111-10, Article 111
Main Authors: Essawi, Mona L, Fateen, Ekram M, Atia, Hanan A, Eissa, Noura R, Aboul-Ezz, Eman H, Ibrahim, Mona M, Hassan, Heba A
Format: Article
Language:English
Subjects:
Age
Amniotic fluid
Biopsy
Births
Diagnosis
Egyptian
Electron microscopy
Enzymes
Ethylenediaminetetraacetic acid
Families & family life
Genes
Genetic aspects
Genetics
GNPTAB gene
Inclusion bodies
Lysosomal enzymes
Medical research
Medicine, Experimental
Methylene blue
Microscopy
ML II
Mucolipidosis
Mutation
Mutations
Next-generation sequencing
NGS
Patients
Phenotypes
Phosphotransferase
Research ethics
X-rays
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Summary:Background Mucolipidosis II (ML II [alpha]/[beta]) 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.
ISSN:1687-157X
2090-5920
DOI:10.1186/s43141-021-00204-4