A Splice Site Mutation in the Human Type I Hair Keratin Gene hHa1 Results in the Expression of a Tailless Keratin Isoform

The study examined a splice site mutation in the human type I hair keratin gene hHa1, affecting about 5% of the population, which resulted in a tailless isoform, hHa1-t. This mutation involved a G-A substitution at the 5′ splice site of intron 6, leading to a 41-kDa protein variant that was 6-kDa smaller than the normal 47-kDa keratin. Despite lacking the nonhelical tail domain, hHa1-t was functional and capable of forming intermediate filaments with type II keratins, indicating that the tail domain was not essential for filament assembly. The mutation was transmitted in an autosomal dominant manner and did not result in any pathological hair phenotype, suggesting that the tailless keratin maintained the structural integrity necessary for normal hair structure.