Hirschsprung病患者由来培養リンパ球において検出された新規エンドセリンB受容体スプライス変異の解析

概要

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Hirschsprung disease is reported to be a heterogeneous genetic disorder involving several genes including the endothelin B receptor (ETBR). To search the mutations of ETBR in Hirschsprung disease, we examined expression of the ETBR gene in lymphoblastoid cells from patients and normal healthy adults, and found a novel mutant transcript. The mutant ETBR gene transcript lacked a 134-bp nucleotide sequence corresponding to exon 5, and some also contained a substitution of G for A at position 950 in exon 4 resulting in an amino acid substitution of arginine for glutamate. This substitution was suspected to be due to RNA editing since it was not present in the genomic sequence. However, the transfection experiments with a minigene containing the region from exon 4 to exon 6 of the ETBR gene did not show any clear evidence to support the RNA editing by double-stranded RNA adenosine deaminase (DRADA). Further, c-myc-tagged mutant ETBR protein was not detected by Western blot analysis. These results showed that the mutant ETBR transcripts are novel splice variants which are not translated.
東京女子医科大学の論文
1999-03-25