A pedigree showing an autosomal dominant inheritance pattern like what is expected in families with<unk> . Regardless of gender or other traits, the probability of each offspring inheriting the affected gene is 50%.<unk>  is caused by a mutation in the ATXN1 gene. This mutation is passed down through an autosomal dominant inheritance pattern, meaning that the disease does not skip generations, at least one parent must have the disease for the children to inherit it, and that the odds of any given child inheriting<unk> , regardless of gender or other phenotypes, is 50% if the affected parent is heterozygous. The ATXN1 gene on chromosome 6 encodes the ataxin<unk>  protein, which is used in signaling pathways and gene regulation, and is heavily expressed in Purkinje neurons. The coding region for Ataxin<unk>  (6p22.3) contains a polyglutamine tract of variable length.<unk>  is present in individuals where the region on at least one copy of chromosome 6 contains 39 or more continuous repeats of glutamine in which more repeats are correlated to earlier onset and faster progression. Histidine interruptions in the polygluatamine tract can mitigate or prevent<unk> .<unk>  is known to exhibit genetic anticipation, where one generation with the disease may exhibit earlier onset and faster progression than the previous generation. This is typically caused by expansions in the polyglutamine tract between generations and is more common in cases of patrilineal inheritance. This non-Mendelian inheritance is similar to that observed in Huntington's disease and is believed to be caused by differences in various mechanisms in gamete production between the sexes that result in increased mosaicism in the male germline. DNA with CAG repeats are prone to forming secondary structures, including hairpin loops and R-loops, which can result in mutations and mosaicism if DNA repair mechanisms fail. These secondary structures cause somatic mosaicism by lagging DNA polymerase in Okazaki fragments and by disrupting DNA mismatch repair, base excision repair, nucleotide excision repair and double strand break repair mechanisms. The mechanism for germline expansions is not well understood, but it is believed that only mismatch repair pathways effect germline instability and the MSH2 repair protein has been linked to expansions in male gametes in mice models.
Spinocerebellar ataxia type 1
Spinocerebellar ataxia type 6
Spinocerebellar ataxia type-13
Autosomal recessive cerebellar ataxia type 1
Metachromatic leukodystrophy
Benign hereditary chorea
Stratton Parker syndrome
Friedreich's ataxia