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. 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. 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.

中文翻译：

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黏脂贮积症Ⅱ四期诊断方案及GNPTAB基因新突变检测

粘脂贮积症 II (ML II α/β) 是一种遗传性溶酶体贮积症，由 GlcNAc 磷酸转移酶缺乏引起，导致多种溶酶体酶的错误靶向。受影响的患者的特征是骨骼畸形和发育迟缓。GNPTAB 基因的纯合或复合杂合突变与临床表现有关。这是第一项在埃及患者队列中表征 ML 潜在遗传学的研究。ML II诊断通过临床评估、酶生化评估、牙龈包涵体电镜检查和GNPTAB基因分子研究在8例患者中使用靶向二代测序panel建立，形成8个不相关的埃及家庭。测序显示 GNPTAB 基因有 3 个突变；外显子 19 中的 1 个新移码突变（c.3488_3488delC）和先前报道的 2 个突变（外显子 13 中的 c.1759C>T 和外显子 19 中的 c.3503_3504delTC）。所有患者的相应突变均为纯合子，父母为近亲。根据既定的四级诊断方案，ML II 是 8 名患者的最终诊断结果。最常见的突变是移码 c.3503_3504delTC 突变，在 5 名患者中发现并与严重表型相关。