Editing Huntington's disease (section)

===Predictive genetic testing===

Because HD follows an autosomal dominant pattern of inheritance, a strong motivation exists for individuals who are at risk of inheriting it to seek a diagnosis. The genetic test for HD consists of a blood test, which counts the numbers of CAG repeats in each of the ''HTT'' alleles.<ref name="pmid15717026">{{cite journal | vauthors = Myers RH | title = Huntington's disease genetics | journal = NeuroRx | volume = 1 | issue = 2 | pages = 255–262 | date = April 2004 | pmid = 15717026 | pmc = 534940 | doi = 10.1602/neurorx.1.2.255 }}</ref> [[Cutoff (reference value)|Cutoffs]] are given as follows:
* At 40 or more CAG repeats, full [[penetrance]] allele (FPA) exists.<ref name=Die-Smulders2013>{{cite journal | vauthors = de Die-Smulders CE, de Wert GM, Liebaers I, Tibben A, Evers-Kiebooms G | title = Reproductive options for prospective parents in families with Huntington's disease: clinical, psychological and ethical reflections | journal = Human Reproduction Update | volume = 19 | issue = 3 | pages = 304–315 | date = May 2013 | pmid = 23377865 | doi = 10.1093/humupd/dms058 | doi-access = free }} {{cite journal | vauthors = de Die-Smulders CE, de Wert GM, Liebaers I, Tibben A, Evers-Kiebooms G | title = Reproductive options for prospective parents in families with Huntington's disease: clinical, psychological and ethical reflections | journal = Human Reproduction Update | volume = 19 | issue = 3 | pages = 304–315 | year = 2013 | pmid = 23377865 | doi = 10.1093/humupd/dms058 | doi-access = free }}</ref> A "[[positive test]]" or "positive result" generally refers to this case. A positive result is not considered a diagnosis, since it may be obtained decades before the symptoms begin. However, a negative test means that the individual does not carry the expanded copy of the gene and will not develop HD.<ref name="lancet07" /> The test will tell a person who originally had a 50% chance of inheriting the disease if their risk goes up to 100% or is eliminated. Persons who test positive for the disease will develop HD sometime within their lifetimes, provided they live long enough for the disease to appear.<ref name="lancet07" />
* At 36 to 39 repeats, incomplete or reduced penetrance allele (RPA) may cause symptoms, usually later in the adult life.<ref name=Die-Smulders2013/> The maximum risk is 60% that a person with an RPA will be symptomatic at age 65, and 70% at 75.<ref name=Die-Smulders2013/>
* At 27 to 35 repeats, intermediate allele (IA), or large normal allele, is not associated with symptomatic disease in the tested individual, but may expand upon further inheritance to give symptoms in offspring.<ref name=Die-Smulders2013/>
* With 26 or fewer repeats, the result is not associated with HD.<ref name=Die-Smulders2013/>

Testing before the onset of symptoms is a life-changing event and a very personal decision.<ref name="lancet07" /> The main reason given for choosing to test for HD is to aid in career and family decisions.<ref name="lancet07" /> Predictive testing for Huntington's disease has been available via linkage analysis (which requires testing multiple family members) since 1986 and via direct mutation analysis since 1993.<ref>{{cite journal | vauthors = Baig SS, Strong M, Rosser E, Taverner NV, Glew R, Miedzybrodzka Z, Clarke A, Craufurd D, Quarrell OW | title = 22 Years of predictive testing for Huntington's disease: the experience of the UK Huntington's Prediction Consortium | journal = European Journal of Human Genetics | volume = 24 | issue = 10 | pages = 1396–1402 | date = October 2016 | pmid = 27165004 | pmc = 5027682 | doi = 10.1038/ejhg.2016.36 }}</ref> At that time, surveys indicated that 50–70% of at-risk individuals would have been interested in receiving testing, but since predictive testing has been offered far fewer choose to be tested.<ref name="pmid23297124">{{cite journal | vauthors = Forrest Keenan K, Simpson SA, Miedzybrodzka Z, Alexander DA, Semper J | title = How do partners find out about the risk of Huntington's disease in couple relationships? | journal = Journal of Genetic Counseling | volume = 22 | issue = 3 | pages = 336–344 | date = June 2013 | pmid = 23297124 | doi = 10.1007/s10897-012-9562-2 | s2cid = 15447709 }}</ref> Over 95% of individuals at risk of inheriting HD do not proceed with testing, mostly because it has no treatment.<ref name="lancet07" /> A key issue is the anxiety an individual experiences about not knowing whether they will eventually develop HD, compared to the impact of a positive result.<ref name="lancet07" /> Irrespective of the result, stress levels are lower two years after being tested, but the risk of suicide is increased after a positive test result.<ref name="lancet07" /> Individuals found to have not inherited the disorder may experience [[survivor guilt]] about family members who are affected.<ref name="lancet07" /> Other factors taken into account when considering testing include the possibility of discrimination and the implications of a positive result, which usually means a parent has an affected gene and that the individual's siblings will be at risk of inheriting it.<ref name="lancet07" /> In one study, genetic discrimination was found in 46% of individuals at risk for Huntington's disease. It occurred at higher rates within personal relationships than health insurance or employment relations.<ref name="pmid20468061">{{cite journal | vauthors = Erwin C, Williams JK, Juhl AR, Mengeling M, Mills JA, Bombard Y, Hayden MR, Quaid K, Shoulson I, Taylor S, Paulsen JS | title = Perception, experience, and response to genetic discrimination in Huntington disease: the international RESPOND-HD study | journal = American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics | volume = 153B | issue = 5 | pages = 1081–1093 | date = July 2010 | pmid = 20468061 | pmc = 3593716 | doi = 10.1002/ajmg.b.31079 }}</ref> [[Genetic counseling]] in HD can provide information, advice and support for initial decision-making, and then, if chosen, throughout all stages of the testing process.<ref name="geneticcounselling">{{cite journal | vauthors = Burson CM, Markey KR | title = Genetic counseling issues in predictive genetic testing for familial adult-onset neurologic diseases | journal = Seminars in Pediatric Neurology | volume = 8 | issue = 3 | pages = 177–186 | date = September 2001 | pmid = 11575847 | doi = 10.1053/spen.2001.26451 }}</ref> Because of the implications of this test, patients who wish to undergo testing must complete three counseling sessions which provide information about Huntington's.<ref name="pmid22114233">{{cite journal | vauthors = Smith JA, Michie S, Stephenson M, Quarrell O | title = Risk Perception and Decision-making Processes in Candidates for Genetic Testing for Huntington's Disease: An Interpretative Phenomenological Analysis | journal = Journal of Health Psychology | volume = 7 | issue = 2 | pages = 131–144 | date = March 2002 | pmid = 22114233 | doi = 10.1177/1359105302007002398 | s2cid = 40182214 }}</ref>

Counseling and guidelines on the use of genetic testing for HD have become models for other genetic disorders, such as autosomal dominant [[cerebellar ataxia]].<ref name="lancet07" /><ref name="pmid12849232">{{cite journal | vauthors = Hayden MR | title = Predictive testing for Huntington's disease: a universal model? | journal = The Lancet. Neurology | volume = 2 | issue = 3 | pages = 141–142 | date = March 2003 | pmid = 12849232 | doi = 10.1016/S1474-4422(03)00317-X | s2cid = 39581496 }}</ref><ref>{{cite journal | vauthors =  | title = Guidelines for the molecular genetics predictive test in Huntington's disease. International Huntington Association (IHA) and the World Federation of Neurology (WFN) Research Group on Huntington's Chorea | journal = Neurology | volume = 44 | issue = 8 | pages = 1533–1536 | date = August 1994 | pmid = 8058167 | doi = 10.1212/WNL.44.8.1533 | s2cid = 28018134 }}</ref> [[Predictive testing|Presymptomatic testing]] for HD has also influenced testing for other illnesses with genetic variants such as [[polycystic kidney]] disease, familial [[Alzheimer's disease]] and [[breast cancer]].<ref name="pmid12849232"/> The European Molecular Genetics Quality Network have published yearly external quality assessment scheme for molecular genetic testing for this disease and have developed best practice guidelines for genetic testing for HD to assist in testing and reporting of results.<ref name=Losekoot2012>{{cite journal | vauthors = Losekoot M, van Belzen MJ, Seneca S, Bauer P, Stenhouse SA, Barton DE | title = EMQN/CMGS best practice guidelines for the molecular genetic testing of Huntington disease | journal = European Journal of Human Genetics | volume = 21 | issue = 5 | pages = 480–486 | date = May 2013 | pmid = 22990145 | pmc = 3641377 | doi = 10.1038/ejhg.2012.200 }}</ref>