Huntington's disease-like 2 (HDL2) in North America and Japan

Russell L. Margolis, Susan E. Holmes, Adam Rosenblatt, Lisa Gourley, Elizabeth O'Hearn, Christopher A. Ross, William K. Seltzer, Ruth H. Walker, Tetsuo Ashizawa, Astrid Rasmussen, Michael Hayden, Elisabeth W. Almqvist, Juliette Harris, Stanley Fahn, Marcy E. MacDonald, Jayalakshmi Mysore, Takayoshi Shimohata, Shoji Tsuji, Nicholas Potter, Kazuhiro Nakaso & 5 others Yoshiki Adachi, Kenji Nakashima, Thomas Bird, Amanda Krause, Penny Greenstein

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Huntington's Disease-like 2 (HDL2) is a progressive, autosomal dominant, neurodegenerative disorder with marked clinical and pathological similarities to Huntington's disease (HD). The causal mutation is a CTG/CAG expansion mutation on chromosome 16q24.3, in a variably spliced exon of junctophilin-3. The frequency of HDL2 was determined in nine independent series of patients referred for HD testing or selected for the presence of an HD-like phenotype in North America or Japan. The repeat length, ancestry, and age of onset of all North American HDL2 cases were determined. The results show that HDL2 is very rare, with a frequency of 0 to 15% among patients in the nine case series with an HD-like presentation who do not have the HD mutation. HDL2 is predominantly, and perhaps exclusively, found in individuals of African ancestry. Repeat expansions ranged from 44 to 57 triplets, with length instability in maternal transmission detected in a repeat of 33 triplets. A younger age of onset is correlated with a longer repeat length (r2 = 0.29, p = 0.0098). The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD-like phenotype.

Original languageEnglish (US)
Pages (from-to)670-674
Number of pages5
JournalAnnals of Neurology
Volume56
Issue number5
DOIs
StatePublished - Nov 1 2004

Fingerprint

Huntington Disease
North America
Japan
Age of Onset
Mutation
Chromosomes
Phenotype
Trinucleotide Repeats
Genetic Testing
Neurodegenerative Diseases
Huntington Disease-Like 2
Exons
Mothers
Guidelines

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Margolis, R. L., Holmes, S. E., Rosenblatt, A., Gourley, L., O'Hearn, E., Ross, C. A., ... Greenstein, P. (2004). Huntington's disease-like 2 (HDL2) in North America and Japan. Annals of Neurology, 56(5), 670-674. https://doi.org/10.1002/ana.20248

Huntington's disease-like 2 (HDL2) in North America and Japan. / Margolis, Russell L.; Holmes, Susan E.; Rosenblatt, Adam; Gourley, Lisa; O'Hearn, Elizabeth; Ross, Christopher A.; Seltzer, William K.; Walker, Ruth H.; Ashizawa, Tetsuo; Rasmussen, Astrid; Hayden, Michael; Almqvist, Elisabeth W.; Harris, Juliette; Fahn, Stanley; MacDonald, Marcy E.; Mysore, Jayalakshmi; Shimohata, Takayoshi; Tsuji, Shoji; Potter, Nicholas; Nakaso, Kazuhiro; Adachi, Yoshiki; Nakashima, Kenji; Bird, Thomas; Krause, Amanda; Greenstein, Penny.

In: Annals of Neurology, Vol. 56, No. 5, 01.11.2004, p. 670-674.

Research output: Contribution to journalArticle

Margolis, RL, Holmes, SE, Rosenblatt, A, Gourley, L, O'Hearn, E, Ross, CA, Seltzer, WK, Walker, RH, Ashizawa, T, Rasmussen, A, Hayden, M, Almqvist, EW, Harris, J, Fahn, S, MacDonald, ME, Mysore, J, Shimohata, T, Tsuji, S, Potter, N, Nakaso, K, Adachi, Y, Nakashima, K, Bird, T, Krause, A & Greenstein, P 2004, 'Huntington's disease-like 2 (HDL2) in North America and Japan', Annals of Neurology, vol. 56, no. 5, pp. 670-674. https://doi.org/10.1002/ana.20248
Margolis RL, Holmes SE, Rosenblatt A, Gourley L, O'Hearn E, Ross CA et al. Huntington's disease-like 2 (HDL2) in North America and Japan. Annals of Neurology. 2004 Nov 1;56(5):670-674. https://doi.org/10.1002/ana.20248
Margolis, Russell L. ; Holmes, Susan E. ; Rosenblatt, Adam ; Gourley, Lisa ; O'Hearn, Elizabeth ; Ross, Christopher A. ; Seltzer, William K. ; Walker, Ruth H. ; Ashizawa, Tetsuo ; Rasmussen, Astrid ; Hayden, Michael ; Almqvist, Elisabeth W. ; Harris, Juliette ; Fahn, Stanley ; MacDonald, Marcy E. ; Mysore, Jayalakshmi ; Shimohata, Takayoshi ; Tsuji, Shoji ; Potter, Nicholas ; Nakaso, Kazuhiro ; Adachi, Yoshiki ; Nakashima, Kenji ; Bird, Thomas ; Krause, Amanda ; Greenstein, Penny. / Huntington's disease-like 2 (HDL2) in North America and Japan. In: Annals of Neurology. 2004 ; Vol. 56, No. 5. pp. 670-674.
@article{048fe03d182f400c80a52a75ee38fd0d,
title = "Huntington's disease-like 2 (HDL2) in North America and Japan",
abstract = "Huntington's Disease-like 2 (HDL2) is a progressive, autosomal dominant, neurodegenerative disorder with marked clinical and pathological similarities to Huntington's disease (HD). The causal mutation is a CTG/CAG expansion mutation on chromosome 16q24.3, in a variably spliced exon of junctophilin-3. The frequency of HDL2 was determined in nine independent series of patients referred for HD testing or selected for the presence of an HD-like phenotype in North America or Japan. The repeat length, ancestry, and age of onset of all North American HDL2 cases were determined. The results show that HDL2 is very rare, with a frequency of 0 to 15{\%} among patients in the nine case series with an HD-like presentation who do not have the HD mutation. HDL2 is predominantly, and perhaps exclusively, found in individuals of African ancestry. Repeat expansions ranged from 44 to 57 triplets, with length instability in maternal transmission detected in a repeat of 33 triplets. A younger age of onset is correlated with a longer repeat length (r2 = 0.29, p = 0.0098). The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD-like phenotype.",
author = "Margolis, {Russell L.} and Holmes, {Susan E.} and Adam Rosenblatt and Lisa Gourley and Elizabeth O'Hearn and Ross, {Christopher A.} and Seltzer, {William K.} and Walker, {Ruth H.} and Tetsuo Ashizawa and Astrid Rasmussen and Michael Hayden and Almqvist, {Elisabeth W.} and Juliette Harris and Stanley Fahn and MacDonald, {Marcy E.} and Jayalakshmi Mysore and Takayoshi Shimohata and Shoji Tsuji and Nicholas Potter and Kazuhiro Nakaso and Yoshiki Adachi and Kenji Nakashima and Thomas Bird and Amanda Krause and Penny Greenstein",
year = "2004",
month = "11",
day = "1",
doi = "10.1002/ana.20248",
language = "English (US)",
volume = "56",
pages = "670--674",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - Huntington's disease-like 2 (HDL2) in North America and Japan

AU - Margolis, Russell L.

AU - Holmes, Susan E.

AU - Rosenblatt, Adam

AU - Gourley, Lisa

AU - O'Hearn, Elizabeth

AU - Ross, Christopher A.

AU - Seltzer, William K.

AU - Walker, Ruth H.

AU - Ashizawa, Tetsuo

AU - Rasmussen, Astrid

AU - Hayden, Michael

AU - Almqvist, Elisabeth W.

AU - Harris, Juliette

AU - Fahn, Stanley

AU - MacDonald, Marcy E.

AU - Mysore, Jayalakshmi

AU - Shimohata, Takayoshi

AU - Tsuji, Shoji

AU - Potter, Nicholas

AU - Nakaso, Kazuhiro

AU - Adachi, Yoshiki

AU - Nakashima, Kenji

AU - Bird, Thomas

AU - Krause, Amanda

AU - Greenstein, Penny

PY - 2004/11/1

Y1 - 2004/11/1

N2 - Huntington's Disease-like 2 (HDL2) is a progressive, autosomal dominant, neurodegenerative disorder with marked clinical and pathological similarities to Huntington's disease (HD). The causal mutation is a CTG/CAG expansion mutation on chromosome 16q24.3, in a variably spliced exon of junctophilin-3. The frequency of HDL2 was determined in nine independent series of patients referred for HD testing or selected for the presence of an HD-like phenotype in North America or Japan. The repeat length, ancestry, and age of onset of all North American HDL2 cases were determined. The results show that HDL2 is very rare, with a frequency of 0 to 15% among patients in the nine case series with an HD-like presentation who do not have the HD mutation. HDL2 is predominantly, and perhaps exclusively, found in individuals of African ancestry. Repeat expansions ranged from 44 to 57 triplets, with length instability in maternal transmission detected in a repeat of 33 triplets. A younger age of onset is correlated with a longer repeat length (r2 = 0.29, p = 0.0098). The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD-like phenotype.

AB - Huntington's Disease-like 2 (HDL2) is a progressive, autosomal dominant, neurodegenerative disorder with marked clinical and pathological similarities to Huntington's disease (HD). The causal mutation is a CTG/CAG expansion mutation on chromosome 16q24.3, in a variably spliced exon of junctophilin-3. The frequency of HDL2 was determined in nine independent series of patients referred for HD testing or selected for the presence of an HD-like phenotype in North America or Japan. The repeat length, ancestry, and age of onset of all North American HDL2 cases were determined. The results show that HDL2 is very rare, with a frequency of 0 to 15% among patients in the nine case series with an HD-like presentation who do not have the HD mutation. HDL2 is predominantly, and perhaps exclusively, found in individuals of African ancestry. Repeat expansions ranged from 44 to 57 triplets, with length instability in maternal transmission detected in a repeat of 33 triplets. A younger age of onset is correlated with a longer repeat length (r2 = 0.29, p = 0.0098). The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD-like phenotype.

UR - http://www.scopus.com/inward/record.url?scp=9144245757&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9144245757&partnerID=8YFLogxK

U2 - 10.1002/ana.20248

DO - 10.1002/ana.20248

M3 - Article

VL - 56

SP - 670

EP - 674

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 5

ER -