Department of Neurosciences, University of Padova, Padova, Italy.
Eur J Hum Genet. 2012 Dec;20(12):1234-9. doi: 10.1038/ejhg.2012.71. Epub 2012 May 2.
Protein-o-mannosyl transferase 1 (POMT1) is a glycosyltransferase involved in α-dystroglycan (α-DG) glycosylation. Clinical phenotype in POMT1-mutated patients ranges from congenital muscular dystrophy (CMD) with structural brain abnormalities, to limb-girdle muscular dystrophy (LGMD) with microcephaly and mental retardation, to mild LGMD. No cardiac involvement has until now been reported in POMT1-mutated patients. We report three patients who harbored compound heterozygous POMT1 mutations and showed left ventricular (LV) dilation and/or decrease in myocardial contractile force: two had a LGMD phenotype with a normal or close-to-normal cognitive profile and one had CMD with mental retardation and normal brain MRI. Reduced or absent α-DG immunolabeling in muscle biopsies were identified in all three patients. Bioinformatic tools were used to study the potential effect of POMT1-detected mutations. All the detected POMT1 mutations were predicted in silico to interfere with protein folding and/or glycosyltransferase function. The report on the patients described here has widened the clinical spectrum associated with POMT1 mutations to include cardiomyopathy. The functional impact of known and novel POMT1 mutations was predicted with a bioinformatics approach, and results were compared with previous in vitro studies of protein-o-mannosylase function.
蛋白甘露糖基转移酶 1（POMT1）是一种参与α- 肌聚糖（α-DG）糖基化的糖基转移酶。POMT1 突变患者的临床表型范围从伴有结构脑异常的先天性肌营养不良症（CMD），到伴有小头畸形和智力迟钝的肢带型肌营养不良症（LGMD），再到轻度 LGMD。到目前为止，尚未在 POMT1 突变患者中报告心脏受累。我们报告了 3 例携带复合杂合 POMT1 突变的患者，他们表现为左心室（LV）扩张和/或心肌收缩力下降：2 例具有 LGMD 表型，认知功能正常或接近正常，1 例具有 CMD 和智力迟钝以及正常的脑 MRI。所有 3 例患者的肌肉活检中均发现α-DG 免疫标记减少或缺失。使用生物信息学工具研究了 POMT1 检测到的突变的潜在影响。所有检测到的 POMT1 突变均在计算机上预测会干扰蛋白质折叠和/或糖基转移酶功能。这里描述的患者报告拓宽了与 POMT1 突变相关的临床谱，包括心肌病。使用生物信息学方法预测了已知和新的 POMT1 突变的功能影响，并将结果与以前关于蛋白质甘露聚糖酶功能的体外研究进行了比较。
