A PKLR Gene Novel Complex Mutation in Erythrocyte Pyruvate Kinase Deficiency Detected by Targeted Sequence Capture and Next Generation Sequencing.
- Author:
Dong-Liang LI
1
;
Jing ZHANG
2
;
Yan-Li LIU
3
;
Bao-Quan JIAO
3
;
Zhi-Wei WANG
3
;
You-Jun WANG
3
;
Wen-Jing LI
3
;
Lan-Fen HOU
3
;
Hong-Mou GUO
3
;
Yu SUN
3
;
Xiao GUO
3
Author Information
- Publication Type:Journal Article
- MeSH: Anemia, Hemolytic, Congenital Nonspherocytic; genetics; Exons; Genotype; High-Throughput Nucleotide Sequencing; Humans; Introns; Mutation; Pyruvate Kinase; deficiency; genetics; Pyruvate Metabolism, Inborn Errors; genetics
- From: Journal of Experimental Hematology 2015;23(5):1464-1468
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the molecular mechanism of erythrocyte pyruvate kinase deficiency (PKD).
METHODSTargeted sequence capture and next-generation sequencing (NGS) were used to detect the regions of exon and exon-intron boundarie of PKLR gene in a clinical suspected PKD patient. The protein function of mutant gene was forecasted by the SIFT and PolyPhen-2 databank, after the mutation of PKLR gene in the patient was detected by the NGS technology, its genotype was confirmed by Sanger sequencing.
RESULTSThe patient was found to have peculiar double heterozygous mutations: 661 G>A (Asp221Asn) of exon 5 and 1528 C>T (Arg510Ter) of exon 10, resulting in amino acid substitution Asp221Asn and Arg510Ter, these mutations were also further confirmed by Sanger sequencing. The complex mutations were infrequent and each of them was able to cause diseases.
CONCLUSIONThe complex mutations of both 661 G>A and 1528 C>T of PKLR gene are the molecular mechanism of PKD. Simultaneous existance of above-mentioned complex mutations in PDK patient was never been previously reported at home and abroad.
