Li Huimin, Gu Ping, Yao Ru-en, Wang Jian, Fu Qihua, Wang Jing
Department of Laboratory Medicine, Shanghai Jiaotong University School of Medicine , Shanghai , China.
Fetal Pediatr Pathol. 2014 Jun;33(3):182-90. doi: 10.3109/15513815.2014.890260. Epub 2014 Mar 6.
Pyruvate kinase deficiency (PKD) is one of the most common enzymatic defects in humans and it is an autosomal recessive disorder causing chronic nonspherocytic hemolytic anemia.
A two-year-old male baby with severe hemolytic anemia and low level of pyruvate kinase (PK) activity was enrolled in this study. All exons of PKLR gene and their flanking sequences were amplified from the patient's genomic DNA using PCR. Bioinformatics software was used to evaluate the functional impacts of the mutations found in this study.
It was here demonstrated that the boy harbored a previously described mutation (c. 941T>C) in exon 7 and a novel mutation (c. 1183 G>C) in exon 9 of PKLR gene. Both mutations led to significant structural alterations and decreased enzymatic activity of PK, as predicted by tool software.
The compound heterozygous mutations in the PKLR gene were the cause of inherited PKD for this patient.
丙酮酸激酶缺乏症（PKD）是人类最常见的酶缺陷之一，是一种常染色体隐性疾病，可导致慢性非球形红细胞溶血性贫血。
本研究纳入一名患有严重溶血性贫血且丙酮酸激酶（PK）活性水平低的两岁男婴。使用聚合酶链反应（PCR）从患者基因组DNA中扩增PKLR基因的所有外显子及其侧翼序列。利用生物信息学软件评估本研究中发现的突变的功能影响。
结果表明，该男孩在PKLR基因的第7外显子中存在一个先前描述的突变（c. 941T>C），在第9外显子中存在一个新突变（c. 1183 G>C）。如工具软件所预测，这两个突变均导致PK的显著结构改变和酶活性降低。
PKLR基因中的复合杂合突变是该患者遗传性PKD的病因。
