<unk>  is inherited in an autosomal dominant pattern.<unk>  <unk>  is a genetic condition that is inherited in an autosomal dominant pattern, meaning each child of an affected individual has a 50% chance of inheriting the disease. The mutation involves satellite DNA, which is tandemly repeated sequences of DNA that do not code for a protein. The repeats implicated in<unk>  are either 3 or 4 nucleotides in length, classified as microsatellites. Disease results from an abnormally increased number of these microsatellites, termed microsatellite expansion.<unk> 1 The microsatellite expansion responsible for<unk> 1 is of cytosine-thymine-guanine (CTG) triplet repeats, termed trinucleotide repeat expansion and classifying<unk> 1 as a one of several trinucleotide repeat disorders. This expansion occurs at the end of the<unk> PK gene, in the 3' untranslated region.<unk> PK is located on the long arm of chromosome 19.<unk> PK codes for<unk>  protein kinase, a protein expressed predominantly in skeletal muscle. Between 5 and 37 repeats is considered normal; between 38 and 49 repeats is considered pre-mutation, and although not producing symptoms, children can have further repeat expansion and symptomatic disease; greater than 50 repeats almost invariably is symptomatic, with some noted exceptions. Longer repeats are usually associated with earlier onset and more severe disease.<unk> PK alleles with greater than 37 repeats are unstable and additional trinucleotide repeats may be inserted during cell division in mitosis and meiosis. Consequently, the children of individuals with premutations or mutations inherit<unk> PK alleles which are longer than their parents and therefore are more likely to be affected or display an earlier onset and greater severity of the condition, a phenomenon known as anticipation. Repeat expansion is generally considered to be a consequence of the incorporation of additional bases as a result of strand slippage during either DNA replication or DNA repair synthesis. Misalignments occurring during homologous recombinational repair, double-strand break repair or during other DNA repair processes likely contribute to trinucleotide repeat expansions in<unk> 1. Paternal transmission of the congenital form is uncommon (13%), possibly due to selection pressures against sperm with expanded repeats, but juvenile or adult-onset is equally transmitted from either parent. Anticipation tends to be less severe than in cases of maternal inheritance. The RNA from the expanded trinucleotide repeat region forms intranucleoplasmic hairpin loops due to the extensive hydrogen bonding between C-G base pairs, and it has been demonstrated that these sequester the splicing regulator MBNL1 to form distinctive foci. A severe form of<unk> 1, congenital<unk> , may appear in newborns of mothers who have<unk> . Congenital<unk>  can also be inherited via the paternal gene, although it is said to be relatively rare. Congenital means that the condition is present from birth.<unk> 2 The microsatellite expansion responsible for<unk> 2 is of cytosine-cytosine-thymine-guanine (CCTG) repeats, classifying it as a tetranucleotide repeat disorder. This expansion occurs in the first intron CNBP gene on chromosome 3. The repeat expansion for<unk> 2 is much larger than for<unk> 1, ranging from 75 to over 11,000 repeats. Like<unk> 1, the size of the microsatellite repeat array lengthens from generation to generation. Unlike<unk> 1, anticipation does not result, as the degree of repeat expansion beyond 75 repeats does not affect the age of onset or disease severity. The repeat expansion produces an RNA transcript that binds to RNA-binding proteins such as MBNL1, as in<unk> 1. Also, repeat expansion likely reduces expression of CNBP, loss of which causes muscle toxicity.
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