A New Kruppel-Like Factor 1 Mutation (c.947G > A or p.C316Y) in Humans Causes beta-Thalassemia Minor

作者：Nitta Takenori^*; Kawano Fumio; Yamashiro Yasuhiro; Takagi Fumiya; Murata Tomoaki; Tanaka Tatehiko; Ferania Mella; Adhiyanto Chris; Hattori Yukio

来源：Hemoglobin, 2015, 39(2): 121-126.

DOI：10.3109/03630269.2015.1008702

• beta-Globin expression
• beta-thalassemia (beta-thal)
• Kruppel-Like Factor 1 (KLF1)
• next-generation sequencing

Here we describe a Japanese patient with mild beta-thalassemia (beta-thal) with an intact beta-globin gene but a new missense mutation of c.947G>A or p.C316Y in the erythroid Kruppel-Like Factor (KLF1) gene which is strongly associated with the expression of the beta-globin gene. The association of the KLF1 mutation with beta-thal, is here described. The p.C316Y mutation occurred at one of the cysteines that constitute the second zinc finger motif of KLF1, and would have changed the zinc finger conformation to impair the DNA binding properties or the promoter function of the beta-globin gene. Our expression study found that the mutant KLF1 gene had a markedly negative effect on the beta-globin gene expression, or 7.0% of that of its normal counterpart. A presumed heterozygous state, or equimolar presence of the mutant and normal KLF1s reduced the expression rate to 70.0% of the normal alone. This degree of the decrease may explain the very mild phenotype of the patient's beta-thal. Furthermore, the patient's whole-exome analysis using next-generation sequencing revealed that the beta-thal defect is caused by only this KLF1 gene mutation. The Hb A(2) and Hb F levels that are frequently elevated in KLF1 mutations were elevated by 4.1 and 1.3%, respectively, in this case. The contribution to their elevation by KLF1: p.C316Y is uncertain.

• 出版日期2015