Mucolipidosis (ML) (OMIM 607840 & 607838) is a rare autosomal recessive inherited disorder that occurs due to the deficiency of golgi enzyme uridine diphosphate (UDP)– N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) responsible for tagging mannose-6-phosphate for proper trafficking of lysosomal enzymes to lysosomes. Variants in GlcNAc-phosphotransferase (GNPTAB (α, β subunits) and GNPTG (γ subunits) are known to result in impaired targeting of lysosomal enzymes leading to Mucolipidosis (ML) Type II or Type III. We analyzed 69 Indian families of MLII/III for clinical features and molecular spectrum and performed in silico analysis for novel variants. We identified 38 pathogenic variants in GNPTAB and 5 pathogenic variants in GNPTG genes including missense, frame shift, deletion, duplication and splice site variations. A total of 26 novel variants were identified in GNPTAB and 4 in GNPTG gene. In silico studies using mutation prediction software like SIFT, Polyphen2 and protein structure analysis further confirmed the pathogenic nature of the novel sequence variants detected in our study. Except for a common variant c.3503_3504delTC in early onset MLII, we could not establish any other significant genotype and phenotype correlation. This is one of the largest studies reported till date on Mucolipidosis II/III in order to identify mutation spectrum and any recurrent mutations specific to the Indian ethnic population. The mutational spectrum information in Indian patients will be useful in better genetic counselling, carrier detection and prenatal diagnosis for patients with ML II/III.

粘液脂病（ML）（OMIM 607840＆607838）是一种罕见的常染色体隐性遗传性疾病，由于高尔基酶尿苷二磷酸（UDP）–负责标记甘露糖6的N-乙酰氨基葡萄糖-1-磷酸转移酶（GlcNAc-磷酸转移酶）缺乏而发生-磷酸盐用于将溶酶体酶适当运输至溶酶体。已知GlcNAc-磷酸转移酶（GNPTAB（α，β亚基）和GNPTG（γ亚基）的变体会导致溶酶体酶的靶向性受损，从而导致II型或III型血脂异常（ML）我们分析了69个印度的MLII / III家族对于临床特征和分子光谱和在计算机芯片上分析新颖变体进行的。我们发现在38个致病变种GNPTAB，并在5个致病变种GNPTG基因包括错义，移码，缺失，重复和剪接位点变异。在GNPTAB中共鉴定出26种新变体，在GNPTG中鉴定出4种基因。在使用突变预测软件（如SIFT，Polyphen2和蛋白质结构分析）进行的计算机模拟研究中，进一步证实了在我们的研究中检测到的新型序列变异的致病性。除了早期发作的MLII中的常见变体c.3503_3504delTC，我们无法建立任何其他重要的基因型和表型相关性。这是迄今为止报道的关于粘液脂血症II / III的最大的研究之一，目的是鉴定突变谱以及印度裔人口特有的任何复发突变。印度患者的突变谱信息将有助于ML II / III患者更好的遗传咨询，携带者检测和产前诊断。