BACKGROUND: Huntington's disease (HD) is a devastating heredoneurodegenerative disorder associated with a wide variety of neurological and psychiatric symptoms caused by an expanded CAG repeat in the HTT gene. The expansion mutation in HTT is dominantly transmitted and codes for a protein named huntingtin (htt). HYPOTHESIS: One hypothesis, according to a multistep mechanism, is that the intergenerational transmission of the normal repeat size causes small, progressive CAG stretch elongations in the general population from one generation to another, until a critical pathological CAG repeat threshold is reached. Mutations may originate in the offspring from paternally transmitted CAG repeats, falling within an intermediate alleles (IA) range of 27 to 35 in repeat length. CONCLUSIONS: There has been emerging evidence that some individuals with IAs might develop an HD phenotype. This presents a challenge for genetic counseling, because these individuals are often reassured that they are "disease free." However, there are many unanswered questions related to the role of IAs in the development of the HD phenotype and in the pathogenesis of HD.
BACKGROUND: Huntington's disease (HD) is a devastating heredoneurodegenerative disorder associated with a wide variety of neurological and psychiatric symptoms caused by an expanded CAG repeat in the HTT gene. The expansion mutation in HTT is dominantly transmitted and codes for a protein named huntingtin (htt). HYPOTHESIS: One hypothesis, according to a multistep mechanism, is that the intergenerational transmission of the normal repeat size causes small, progressive CAG stretch elongations in the general population from one generation to another, until a critical pathological CAG repeat threshold is reached. Mutations may originate in the offspring from paternally transmitted CAG repeats, falling within an intermediate alleles (IA) range of 27 to 35 in repeat length. CONCLUSIONS: There has been emerging evidence that some individuals with IAs might develop an HD phenotype. This presents a challenge for genetic counseling, because these individuals are often reassured that they are "disease free." However, there are many unanswered questions related to the role of IAs in the development of the HD phenotype and in the pathogenesis of HD.
Authors: Jessica Raper; Steven Bosinger; Zachary Johnson; Gregory Tharp; Sean P Moran; Anthony W S Chan Journal: Brain Behav Immun Date: 2016-07-07 Impact factor: 7.217
Authors: Christopher A Ross; Elizabeth H Aylward; Edward J Wild; Douglas R Langbehn; Jeffrey D Long; John H Warner; Rachael I Scahill; Blair R Leavitt; Julie C Stout; Jane S Paulsen; Ralf Reilmann; Paul G Unschuld; Alice Wexler; Russell L Margolis; Sarah J Tabrizi Journal: Nat Rev Neurol Date: 2014-03-11 Impact factor: 42.937
Authors: Macarena Solís-Maldonado; María Paz Miró; Aníbal I Acuña; Adriana Covarrubias-Pinto; Anitsi Loaiza; Gonzalo Mayorga; Felipe A Beltrán; Carlos Cepeda; Michael S Levine; Ilona I Concha; Luis Federico Bátiz; Mónica A Carrasco; Maite A Castro Journal: CNS Neurosci Ther Date: 2018-04 Impact factor: 5.243
Authors: Anthony W S Chan; Jie Jiang; Yiju Chen; Chunxia Li; Melinda S Prucha; Yijuan Hu; Tim Chi; Sean Moran; Tayeb Rahim; Shihua Li; Xiaojiang Li; Stuart M Zola; Claudia M Testa; Hui Mao; Rosa Villalba; Yoland Smith; Xiaodong Zhang; Jocelyne Bachevalier Journal: PLoS One Date: 2015-05-12 Impact factor: 3.240
Authors: Tânia R Soares; Sara D Reis; Brígida R Pinho; Michael R Duchen; Jorge M A Oliveira Journal: Ageing Res Rev Date: 2018-11-28 Impact factor: 10.895