Mutant huntingtin messenger RNA containing rs72239206 (mHTT mRNA (rs72239206))

Mutant huntingtin (HTT) messenger RNA containing the rs72239206 polymorphism is a therapeutic target for the allele-selective treatment of Huntington's Disease (HD). HD is a neurodegenerative disorder caused by a CAG repeat expansion in the HTT gene, which produces a toxic mutant protein. Because the wild-type huntingtin protein is essential for neuronal health, therapeutic strategies aim to selectively degrade the mutant transcript while sparing the wild-type version. The rs72239206 variant is a 4-base pair deletion (ΔACTT) located in intron 22 of the HTT gene and is a defining marker of the A1 haplotype, which is highly prevalent among HD patients of European descent. Antisense oligonucleotides (ASOs) designed to target this specific sequence trigger RNase H-mediated degradation of the pre-mRNA, effectively reducing the levels of toxic mutant protein. This approach provides a high degree of selectivity, as the target sequence is absent in the wild-type allele of heterozygous patients.

Other names

Mutant HTT pre-mRNA (rs72239206)rs72239206-containing HTT transcriptA1 haplotype-specific HTT mRNAΔACTT HTT variantHuntingtin A1 haplotype marker

Allele-selective RNase H-mediated degradation of mutant HTT pre-mRNA