Case reports of juvenile GM1 gangliosidosisis type II caused by mutation in GLB1 gene

作者：Parvaneh Karimzadeh, Samaneh Naderi, Farzaneh Modarresi, Hassan Dastsooz, Hamid Nemati, T. Farokhashtiani, Bibi Shahin Shamsian, Soroor Inaloo, Mohammad Ali Faghihi · 发表于：BMC Medical Genetics · 年份：2017 · DOI：10.1186/s12881-017-0417-4 · 被引用次数：24 · 研究领域：Lysosomal Storage Disorders Research、Glycosylation and Glycoproteins Research、Glycogen Storage Diseases and Myoclonus

BACKGROUND: Type II or juvenile GM1-gangliosidosis is an autosomal recessive lysosomal storage disorder, which is clinically distinct from infantile form of the disease by the lack of characteristic cherry-red spot and hepatosplenomegaly. The disease is characterized by slowly progressive neurodegeneration and mild skeletal changes. Due to the later age of onset and uncharacteristic presentation, diagnosis is frequently puzzled with other ataxic and purely neurological disorders. Up to now, 3-4 types of GM1-gangliosidosis have been reported and among them type I is the most common phenotype with the age of onset around 6 months. Various forms of GM1-gangliosidosis are caused by GLB1 gene mutations but severity of the disease and age of onset are directly related to the position and the nature of deleterious mutations. However, due to its unique genetic cause and overlapping clinical features, some researchers believe that GM1 gangliosidosis represents an overlapped disease spectrum instead of four distinct types. CASE PRESENTATION: Here, we report a less frequent type of autosomal recessive GM1 gangliosidosis with perplexing clinical presentation in three families in the southwest part of Iran, who are unrelated but all from "Lurs" ethnic background. To identify disease-causing mutations, Whole Exome Sequencing (WES) utilizing next generation sequencing was performed. Four patients from three families were investigated with the age of onset around 3 years old. Clinical presen...