The huntingtin gene (HTT) pathogenic cytosine-adenine-guanine (CAG) repeat expansion responsible for Huntington disease (HD) is phased with single nucleotide polymorphisms (SNPs), providing targets for allele-selective treatments.

This prospective observational study defined the frequency at which rs362307 (SNP1) or rs362331 (SNP2) was found on the same allele with pathogenic CAG expansions.

Across 7 US sites, 202 individuals with HD provided blood samples that were processed centrally to determine the number and size of CAG repeats, presence and heterozygosity of SNPs, and whether SNPs were present on the mutant HTT allele using long-read sequencing and phasing.

Heterozygosity of SNP1 and/or SNP2 was identified in 146 (72%) individuals. The 2 polymorphisms were associated only with the mHTT allele in 61% (95% high density interval: 55%, 67%) of individuals.

These results are consistent with previous reports and demonstrate the feasibility of genotyping, phasing, and targeting of HTT SNPs for personalized treatment of HD.

导致亨廷顿病 (HD)的亨廷顿基因 ( HTT ) 致病性胞嘧啶-腺嘌呤-鸟嘌呤 (CAG) 重复扩增与单核苷酸多态性 (SNP) 相结合，为等位基因选择性治疗提供靶点。

这项前瞻性观察性研究定义了在具有致病性 CAG 扩增的相同等位基因上发现 rs362307 (SNP1) 或 rs362331 (SNP2) 的频率。

在美国的 7 个地点，202 名 HD 患者提供了血液样本，这些样本经过集中处理以确定 CAG 重复的数量和大小、SNP 的存在和杂合性，以及 SNP 是否存在于突变HTT等位基因上，使用长读长测序和定相。

SNP1 和/或 SNP2 的杂合性在 146 名 (72%) 个体中被发现。2 个多态性仅与 61%（95% 高密度区间：55%、67%）的个体中的 m HTT等位基因相关。

这些结果与以前的报告一致，并证明了HTT SNP 的基因分型、定相和靶向用于 HD 个性化治疗的可行性。