HTT and Huntington disease: Despite these limitations, we know that homozygous Huntington's disease patients without wild-type HTT remain symptom-free for many years and that individuals with a loss-of-function (LoF) HTT variant have no clinical phenotype.5-7 Conversely, individuals with two HTT LoF alleles have a neurodevelopmental phenotype8 and HTT-knockout mice die in utero.