Expanding the genetic spectrum of Mucolipidosis in Egyptian patients: Recurrent and novel GNPTAB and GNPTG genes variants

Eissa, Noura R.; Essawi, Mona L.; Abdel-Salam, Ghada M.H.; Hassan, Heba A.; Fateen, Ekram M.; Temtamy, Samia A.

doi:10.21608/MXE.2023.283877

Expanding the genetic spectrum of Mucolipidosis in Egyptian patients: Recurrent and novel GNPTAB and GNPTG genes variants

Document Type : Original Article

Authors

¹ Department of Medical Molecular Genetics, Human Genetics and Genome Research Institute, Dokki, Egypt.

² Department of Clinical Genetics, Human Genetics and Genome Research Institute, Dokki, Egypt.

³ Department of Biochemical Genetics, Human Genetics and Genome Research Institute, Dokki, Egypt.

10.21608/MXE.2023.283877

Abstract

Mucolipidosis term describes several clinical conditions that combine features of both mucopolysaccharidoses and sphingolipidoses. Mucolipidosis typeII (MLII) and MLIII are two forms of a rare autosomal recessive lysosomal storage disorder. Both result from deficiency of the N- acetylglucosamine (GlcNAc)-1-phospho- transferase enzyme. This enzyme is a hexameric complex; 2α, 2β and 2γ encoded by two genes; GNPTAB & GNPTG gene. In this study, we report the underlying genetics of 4 different ML Egyptian patients who were recruited according to their clinical presentations, and β-Hexosaminindase -A enzyme activity assay. Whole exome sequencing for the four patients was carried out revealing 4 different mutations with all patients homozygous for their corresponding mutations. Two frameshift mutations were found in GNPTAB gene; c.2693dupA in exons 13 & c.3503_3504delTC in exon 19. The other two mutations were mapped to the GNPTG gene; a novel nonsense mutation c.658A>T in exon 4, and the splice site mutation c.233+1G>A. both mutations were associated with mild phenotype.

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