Coppens Sandra, Koralkova Pavla, Aeby Alec, Mojzikova Renata, Deconinck Nicolas, Kadhim Hazim, van Wijk Richard
Neuromuscular Reference Centre, Department of Pediatric Neurology, Hôpital Erasme, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium; Neuromuscular Reference Centre, Department of Pediatric Neurology, Queen Fabiola Children's University Hospital, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Biology, Faculty of Medicine and Dentistry, Palacký University Olomouc, Olomouc, Czech Republic.
Neuromuscul Disord. 2016 Mar;26(3):207-10. doi: 10.1016/j.nmd.2015.11.008. Epub 2015 Nov 30.
We report two brothers with mild intellectual deficiency, exercise intolerance, rhabdomyolysis, seizures and no hemolysis. Phosphoglycerate kinase (PGK) activity was strongly decreased in their red blood cells. Subsequent molecular analysis of PGK1 revealed hemizygosity for a novel mutation c.756 + 3A > G, in intron 7. Analysis of the effect of this mutation on pre-mRNA processing demonstrated markedly decreased levels of normal PGK1 mRNA. In addition, the c.756 + 3A > G change resulted in abnormally spliced transcripts. If translated, these transcripts mostly encode for C-terminally truncated proteins. The consequences of the c.756 + 3A > G mutation is discussed, as well as the genotype-to-phenotype correlation with regard to previously described mutations (PGK Fukuroi and PGK Antwerp), which also result in C-terminal truncated proteins.
我们报告了两兄弟，他们有轻度智力缺陷、运动不耐受、横纹肌溶解、癫痫发作且无溶血现象。他们红细胞中的磷酸甘油酸激酶（PGK）活性显著降低。随后对PGK1进行分子分析，发现第7内含子存在一个新的突变c.756 + 3A > G的半合子状态。对该突变对前体mRNA加工影响的分析表明，正常PGK1 mRNA水平显著降低。此外，c.756 + 3A > G的变化导致转录本异常剪接。如果这些转录本被翻译，大多会编码C末端截短的蛋白质。本文讨论了c.756 + 3A > G突变的后果，以及与先前描述的同样导致C末端截短蛋白质的突变（PGK福留井型和PGK安特卫普型）的基因型-表型相关性。
