Huntington disease in subjects from an Israeli Karaite community carrying alleles of intermediate and expanded CAG repeats in the HTT gene

Huntington disease or phenocopy?

Yuval O. Herishanu, Ruti Parvari, Yaakov Pollack, Ilan Shelef, Batia Marom, Tiziana Martino, Milena Cannella, Ferdinando Squitieri

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

We report a cluster of patients from a Karaite Jew community with a movement disorder suggestive of Huntington disease (HD), in some cases associated with repeat lengths below the edge of 36 CAG repeats. The study describes the clinical and genetic features of four patients who were followed over several years. Patients belonged to an inbred family in whom progressive chorea, manifesting predominantly with dystonia and cerebellar features, developed during middle age. Although severe psychiatric symptoms ultimately developed in two of the four patients, cognitive function remained reasonably well preserved in all of them even after several disease years. Moderate cognitive deficits were limited to the visuomotor organization and abstract thinking subtests in three of the four patients. Qualitative brain imaging showed atrophy of brain predominantly involving cortex and cerebellum. Genetic testing revealed a variable mutation penetrance among family members, some affected members showing an upper allele size ranging from 34 to 49, whereas others remained unaffected despite the presence of the full mutation beyond 40 CAG repeats. Co-morbidity with recessive hereditary inclusion body myopathy was found in two subjects from one family. Although the main diagnosis of HD remains to be confirmed by further neuropathological studies, these cases may suggest that HD could manifest with as few as 34 CAG repeats, in some geographic areas, the disease phenotype most probably being influenced by additional, as yet unidentified, genes.

Original languageEnglish
Pages (from-to)143-146
Number of pages4
JournalJournal of the Neurological Sciences
Volume277
Issue number1-2
DOIs
Publication statusPublished - Feb 15 2009

Fingerprint

Huntington Disease
Alleles
Genes
Jews
Chorea
Mutation
Penetrance
Dystonia
Movement Disorders
Genetic Testing
Neuroimaging
Cerebellum
Cognition
Atrophy
Psychiatry
Huntington Disease-Like Syndrome
Organizations
Morbidity
Phenotype
Brain

Keywords

  • Huntington disease mutation penetrance
  • Huntington disease phenocopies
  • Huntington disease pre-mutations
  • Karaite community
  • Movement disorder

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Huntington disease in subjects from an Israeli Karaite community carrying alleles of intermediate and expanded CAG repeats in the HTT gene : Huntington disease or phenocopy? / Herishanu, Yuval O.; Parvari, Ruti; Pollack, Yaakov; Shelef, Ilan; Marom, Batia; Martino, Tiziana; Cannella, Milena; Squitieri, Ferdinando.

In: Journal of the Neurological Sciences, Vol. 277, No. 1-2, 15.02.2009, p. 143-146.

Research output: Contribution to journalArticle

@article{ba1c9d13663b45048035a680ab7468ff,
title = "Huntington disease in subjects from an Israeli Karaite community carrying alleles of intermediate and expanded CAG repeats in the HTT gene: Huntington disease or phenocopy?",
abstract = "We report a cluster of patients from a Karaite Jew community with a movement disorder suggestive of Huntington disease (HD), in some cases associated with repeat lengths below the edge of 36 CAG repeats. The study describes the clinical and genetic features of four patients who were followed over several years. Patients belonged to an inbred family in whom progressive chorea, manifesting predominantly with dystonia and cerebellar features, developed during middle age. Although severe psychiatric symptoms ultimately developed in two of the four patients, cognitive function remained reasonably well preserved in all of them even after several disease years. Moderate cognitive deficits were limited to the visuomotor organization and abstract thinking subtests in three of the four patients. Qualitative brain imaging showed atrophy of brain predominantly involving cortex and cerebellum. Genetic testing revealed a variable mutation penetrance among family members, some affected members showing an upper allele size ranging from 34 to 49, whereas others remained unaffected despite the presence of the full mutation beyond 40 CAG repeats. Co-morbidity with recessive hereditary inclusion body myopathy was found in two subjects from one family. Although the main diagnosis of HD remains to be confirmed by further neuropathological studies, these cases may suggest that HD could manifest with as few as 34 CAG repeats, in some geographic areas, the disease phenotype most probably being influenced by additional, as yet unidentified, genes.",
keywords = "Huntington disease mutation penetrance, Huntington disease phenocopies, Huntington disease pre-mutations, Karaite community, Movement disorder",
author = "Herishanu, {Yuval O.} and Ruti Parvari and Yaakov Pollack and Ilan Shelef and Batia Marom and Tiziana Martino and Milena Cannella and Ferdinando Squitieri",
year = "2009",
month = "2",
day = "15",
doi = "10.1016/j.jns.2008.11.005",
language = "English",
volume = "277",
pages = "143--146",
journal = "Journal of the Neurological Sciences",
issn = "0022-510X",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Huntington disease in subjects from an Israeli Karaite community carrying alleles of intermediate and expanded CAG repeats in the HTT gene

T2 - Huntington disease or phenocopy?

AU - Herishanu, Yuval O.

AU - Parvari, Ruti

AU - Pollack, Yaakov

AU - Shelef, Ilan

AU - Marom, Batia

AU - Martino, Tiziana

AU - Cannella, Milena

AU - Squitieri, Ferdinando

PY - 2009/2/15

Y1 - 2009/2/15

N2 - We report a cluster of patients from a Karaite Jew community with a movement disorder suggestive of Huntington disease (HD), in some cases associated with repeat lengths below the edge of 36 CAG repeats. The study describes the clinical and genetic features of four patients who were followed over several years. Patients belonged to an inbred family in whom progressive chorea, manifesting predominantly with dystonia and cerebellar features, developed during middle age. Although severe psychiatric symptoms ultimately developed in two of the four patients, cognitive function remained reasonably well preserved in all of them even after several disease years. Moderate cognitive deficits were limited to the visuomotor organization and abstract thinking subtests in three of the four patients. Qualitative brain imaging showed atrophy of brain predominantly involving cortex and cerebellum. Genetic testing revealed a variable mutation penetrance among family members, some affected members showing an upper allele size ranging from 34 to 49, whereas others remained unaffected despite the presence of the full mutation beyond 40 CAG repeats. Co-morbidity with recessive hereditary inclusion body myopathy was found in two subjects from one family. Although the main diagnosis of HD remains to be confirmed by further neuropathological studies, these cases may suggest that HD could manifest with as few as 34 CAG repeats, in some geographic areas, the disease phenotype most probably being influenced by additional, as yet unidentified, genes.

AB - We report a cluster of patients from a Karaite Jew community with a movement disorder suggestive of Huntington disease (HD), in some cases associated with repeat lengths below the edge of 36 CAG repeats. The study describes the clinical and genetic features of four patients who were followed over several years. Patients belonged to an inbred family in whom progressive chorea, manifesting predominantly with dystonia and cerebellar features, developed during middle age. Although severe psychiatric symptoms ultimately developed in two of the four patients, cognitive function remained reasonably well preserved in all of them even after several disease years. Moderate cognitive deficits were limited to the visuomotor organization and abstract thinking subtests in three of the four patients. Qualitative brain imaging showed atrophy of brain predominantly involving cortex and cerebellum. Genetic testing revealed a variable mutation penetrance among family members, some affected members showing an upper allele size ranging from 34 to 49, whereas others remained unaffected despite the presence of the full mutation beyond 40 CAG repeats. Co-morbidity with recessive hereditary inclusion body myopathy was found in two subjects from one family. Although the main diagnosis of HD remains to be confirmed by further neuropathological studies, these cases may suggest that HD could manifest with as few as 34 CAG repeats, in some geographic areas, the disease phenotype most probably being influenced by additional, as yet unidentified, genes.

KW - Huntington disease mutation penetrance

KW - Huntington disease phenocopies

KW - Huntington disease pre-mutations

KW - Karaite community

KW - Movement disorder

UR - http://www.scopus.com/inward/record.url?scp=58149457367&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149457367&partnerID=8YFLogxK

U2 - 10.1016/j.jns.2008.11.005

DO - 10.1016/j.jns.2008.11.005

M3 - Article

VL - 277

SP - 143

EP - 146

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

SN - 0022-510X

IS - 1-2

ER -