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. 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.

Genomics in Egypt: Current Status and Future Aspects

“…It is noteworthy that there are continuous international collaborations between the aforementioned Institutions; NRC and MRI and research teams worldwide in attempt to reach the correct diagnosis and unravel the etiology and pathogenesis of rare disorders and identify causative mutations implicated in rare genetic syndromes. These research studies are either conducted on a cohort or per individual case and many of the past studies solved many cases and led to very promising and interesting results in the studied rare genetic syndromes in different genetic subspecialities; neuromuscular disorders, growth disorders, ciliopathies, ocular anomalies, congenital heart diseases, skeletal disorders, dental genetic abnormalities, inherited metabolic disorders, craniofacial disorders, dermatological anomalies and other variable rare genetic disorders with multiple congenital anomalies or disorders with underlying chromosomal aberrations or microdeletions ( Toomes et al, 1999 ; Zaki et al, 2007 ; Bielas et al, 2009 ; Handley et al, 2013 ; Rice et al, 2013 ; Traverso et al, 2013 ; Abdalla et al, 2014 ; Novarino et al, 2014 ; Abdalla et al, 2015 ; El-Hattab et al, 2016 ; Scott et al, 2016 ; Seifi et al, 2016 ; Abdalla et al, 2017 ; Fassad et al, 2018 ; Maddirevula et al, 2018 ; Patel et al, 2018 ; Fassad et al, 2020a ; Fassad et al, 2020b ; Chatron et al, 2020 ; Nabil et al, 2020 ; Shamseldin et al, 2020 ; Donato et al, 2021 ; Essawi et al, 2021 ; Horn et al, 2021 ; Meyer et al, 2021 ; Patel et al, 2021 ; Thomas et al, 2021 ). Moreover, several clinical genetic studies on categories of syndromes or rare disorders were conducted in Egypt.…”