{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T23:30:38Z","timestamp":1772839838741,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2010,2,11]],"date-time":"2010-02-11T00:00:00Z","timestamp":1265846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2010,10]]},"abstract":"<jats:p>Sequeiros J, Ramos EM, Cerqueira J, Costa MC, Sousa A, Pinto\u2010Basto J, Alonso I. Large normal and reduced penetrance alleles in Huntington disease: instability in families and frequency at the laboratory, at the clinic and in the population.<\/jats:p><jats:p>Large normal (\u2018intermediate\u2019) alleles may produce <jats:italic>de novo<\/jats:italic> expansions in Huntington disease; nevertheless, there is very little evidence about their population prevalence and impact in daily practice, and there are conflicting reports about the extent of their instability. We estimated the frequency of large normal alleles (27\u201335 CAGs) and of reduced penetrance alleles (36\u201339 CAGs), as well as the frequency of genotypes carrying them, in (i) a diagnostic laboratory, (ii) a genetic counselling clinic and (iii) the general population. Large normal alleles were present in 6% of a large control sample, 7% of consultands who took pre\u2010symptomatic testing and 7% of samples in the laboratory. Reduced penetrance alleles were found in 1 of 1772 control chromosomes (0.1% of individuals), 5% of 146 pre\u2010symptomatic testees and over 2% of 1214 diagnostic samples (350 families). All 16 alleles sized 27\u201332 CAGs seemed to be transmitted stably; alleles \u2265 36 repeats were unstable in five families. Seven small full penetrance alleles contracted into the reduced penetrance range, but none into the large normal range. Evidence showed that large normal alleles are relatively frequent and that those with reduced penetrance are not a rare event, either at the laboratory or the clinic. This reinforces the need to understand the genomic context of repeat instability in each family and population.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2010.01388.x","type":"journal-article","created":{"date-parts":[[2010,2,11]],"date-time":"2010-02-11T10:07:40Z","timestamp":1265882860000},"page":"381-387","source":"Crossref","is-referenced-by-count":61,"title":["Large normal and reduced penetrance alleles in Huntington disease: instability in families and frequency at the laboratory, at the clinic and in the population"],"prefix":"10.1111","volume":"78","author":[{"given":"J","family":"Sequeiros","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"EM","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Cerqueira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MC","family":"Costa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Sousa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Pinto\u2010Basto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I","family":"Alonso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,9,6]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/301846"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201055"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0893-398"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0893-387"},{"key":"e_1_2_6_7_2","first-page":"1202","article-title":"The likelihood of being affected with Huntington disease by a particular age, for a specific CAG size","volume":"60","author":"Brinkman RR","year":"1997","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2004.00241.x"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.31.5.377"},{"key":"e_1_2_6_10_2","first-page":"343","article-title":"Sex\u2010dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes","volume":"57","author":"Kremer B","year":"1995","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.050930"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1093-174"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1093-168"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30826"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30970"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-005-0343-8"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.8.1533"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.3.1215"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.1.65"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.2.301"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32901"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.9.1519"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30261"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1610"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.02.003"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1399-0004.2010.01388.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1399-0004.2010.01388.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T22:21:44Z","timestamp":1698790904000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1399-0004.2010.01388.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,9,6]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2010,10]]}},"alternative-id":["10.1111\/j.1399-0004.2010.01388.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1399-0004.2010.01388.x","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,9,6]]}}}