not told to stop growing. experiments in yeast and bacteria help to show characteristics of microsatellites that may contribute to defective dna mismatch repair. these include the length of the microsatellite, the makeup of the genetic material and how pure the repeats are. based on experimental results longer microsatellites have a higher rate of frameshift mutations. the flanking dna can also contribute to frameshift mutations. in prostate cancer a frameshift mutation changes the open reading frame (orf) and prevents apoptosis from occurring. this leads to an unregulated growth of the tumor. while there are environmental factors that contribute to the progression of prostate cancer, there is also a genetic component. during testing of coding regions to identify mutations, 116 genetic variants were discovered, including 61 frameshift mutations. there are over 500 mutations on chromosome 17 that seem to play a role in the development of breast and ovarian cancer in the brca1 gene, many of which are frameshift. crohn's disease crohn's disease has an association with the nod2 gene. the mutation is an insertion of a cytosine at position 3020. this leads to a premature stop codon, shortening the protein that is supposed to be transcribed. when the protein is able to form normally, it responds to bacterial liposaccharides, where the 3020insc mutation prevents the protein from being responsive. cystic fibrosis cystic fibrosis (cf) is a disease based on mutations in the cf transmembrane conductance regulator (cftr) gene. there are over 1500 mutations identified, but not all cause the disease. most cases of cystic fibrosis are a result of the ∆f508 mutation, which deletes the entire amino acid. two frameshift mutations are of interest in diagnosing cf, cf1213delt and cf1154-instc. both of these mutations commonly occur in tandem with at least one other mutation. they both lead to a small decrease in the function of the lungs and occur in about 1% of patients tested. these mutations were identified through sanger sequencing. hiv main article: hiv/aids ccr5 is one of the cell entry co-factors associated with hiv, most frequently involved with nonsyncytium-inducing strains, is most apparent in hiv patients as opposed to aids patients. a 32 base pair deletion in ccr5 has been identified as a mutation that negates the likelihood of an hiv infection. this region on the open reading frame orf contains a frameshift mutation leading to a premature stop codon. this leads to the loss of the hiv-coreceptor function in vitro. ccr5-1 is considered the wild type and ccr5-2 is considered to be the mutant allele. those with a heterozygous mutation for the ccr5 were less susceptible to the development of hiv. in a study, despite high exposure to the hiv virus, there was no one homozygous for the ccr5 mutation that tested positive for hiv. tay–sachs disease tay–sachs disease is a fatal disease affecting the central nervous system. it is most frequently found in infants and small children. disease progression begins in the womb but symptoms do not appear until approximately 6 months of age. there is no cure for the disease. mutations in the β-hexosaminidase a (hex a) gene are known to affect the onset of tay-sachs, with 78 mutations of different types being described, 67 of which are known to cause disease. most of the mutations observed (65/78) are single base substitutions or snps, 11 deletions, 1 large and 10 small, and 2 insertions. 8 of the observed mutations are frameshift, 6 deletions and 2 insertions. a 4 base pair insertion in exon 11 is observed in 80% of tay-sachs disease presence in the ashkenazi jewish population. the frameshift mutations lead to an early stop codon which is known to play a role in the disease in infants. delayed onset disease appears to be caused by 4 different mutations, one being a 3 base pair deletion. smith–magenis syndrome smith–magenis syndrome (sms) is a complex syndrome involving intellectual disabilities, sleep disturbance, behavioural problems, and a variety of craniofacial, skeletal, and visceral anomalies. the majority of sms cases harbor an ~3.5 mb common deletion that encompasses the retinoic acid induced-1 (rai1) gene. other cases illustrate variability in the sms phenotype not previously shown for rai1 mutation, including hearing loss, absence of self-abusive behaviours, and mild global delays. sequencing of rai1 revealed mutation of a heptamericc-tract (ccccccc) in exon 3 resulting in frameshift mutations. of the seven reported frameshift mutations occurring in poly c-tracts in rai1, four cases (~57%) occur at this heptameric c-tract. the results indicate that this heptameric c-tract is a preferential recombination hotspot insertion/deletions (snindels) and therefore a primary target for analysis in patients suspected for mutations in rai1. hypertrophic cardiomyopathy hypertrophic cardiomyopathy is the most common cause of sudden death in young people, including trained athletes, and is caused by mutations in genes encoding proteins of the cardiac sarcomere. mutations in the troponin c gene (tnnc1) are a rare genetic cause of hypertrophic cardiomyopathy. a recent study has indicated that a frameshift mutation (c.363dupg or p.gln122alafsx30) in troponin c was the cause of hypertrophic cardiomyopathy (and sudden cardiac death) in a 19-year-old male. cures finding a cure for the diseases caused by frameshift mutations is rare. research into this is ongoing. one example is a primary immunodeficiency (pid), an inherited condition which can lead to an increase in infections. there are 120 genes and 150 mutations that play a role in primary immunodeficiencies. the standard treatment is currently gene therapy, but this is a highly risky treatment and can often lead to other diseases, such as leukemia. gene therapy procedures include modifying the zinc fringer nuclease fusion protein, cleaving both ends of the mutation, which in turn removes it from the sequence. antisense-oligonucleotide mediated exon skipping is another possibility for duchenne muscular dystrophy. this process allows for passing over the mutation so that the rest of the sequence remains in frame and the function of the protein stays intact. this, however, does not cure the disease, just treats symptoms, and is only practical in structural proteins or other repetitive genes. a third form of repair is revertant mosaicism, which is naturally occurring by creating a reverse mutation or a mutation at a second site that corrects the reading frame. this reversion may happen by intragenic recombination, mitotic gene conversion, second site dna slipping or site-specific reversion. this is possible in several diseases, such as x-linked severe combined immunodeficiency (scid), wiskott–aldrich syndrome, and bloom syndrome. there are no drugs or other pharmacogenomic methods that help with pids. a european patent (ep1369126a1) in 2003 by bork records a method used for prevention of cancers and for the curative treatment of cancers and precancers such as dna-mismatch repair deficient (mmr) sporadic tumours and hnpcc associated tumours. the idea is to use immunotherapy with combinatorial mixtures of tumour-specific frameshift mutation-derived peptides to elicit a cytotoxic t-cell response specifically directed against tumour cells.