Clinical manifestations of intermediate allele carriers in Huntington disease

Esther Cubo, María A. Ramos-Arroyo, Saul Martinez-Horta, Asunción Martínez-Descalls, Sara Calvo, Cecilia Gil-Polo, European HD Network

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry.

METHODS: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores.

RESULTS: Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p = 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p = 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p = 0.002).

CONCLUSIONS: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling.

CLINICALTRIALSGOV IDENTIFIER: NCT01590589.

Original languageEnglish
Pages (from-to)571-578
Number of pages8
JournalNeurology
Volume87
Issue number6
Early online date8 Jul 2016
DOIs
Publication statusPublished - 9 Aug 2016

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Huntington Disease
Alleles
Regression Analysis
Outcome Assessment (Health Care)
Chorea
Genetic Counseling
Registries
Linear Models
Quality of Life
Phenotype

Cite this

Cubo, E., Ramos-Arroyo, M. A., Martinez-Horta, S., Martínez-Descalls, A., Calvo, S., Gil-Polo, C., & European HD Network (2016). Clinical manifestations of intermediate allele carriers in Huntington disease. Neurology, 87(6), 571-578. https://doi.org/10.1212/WNL.0000000000002944

Clinical manifestations of intermediate allele carriers in Huntington disease. / Cubo, Esther; Ramos-Arroyo, María A.; Martinez-Horta, Saul; Martínez-Descalls, Asunción; Calvo, Sara; Gil-Polo, Cecilia; European HD Network.

In: Neurology, Vol. 87, No. 6, 09.08.2016, p. 571-578.

Research output: Contribution to journalArticle

Cubo, E, Ramos-Arroyo, MA, Martinez-Horta, S, Martínez-Descalls, A, Calvo, S, Gil-Polo, C & European HD Network 2016, 'Clinical manifestations of intermediate allele carriers in Huntington disease', Neurology, vol. 87, no. 6, pp. 571-578. https://doi.org/10.1212/WNL.0000000000002944
Cubo E, Ramos-Arroyo MA, Martinez-Horta S, Martínez-Descalls A, Calvo S, Gil-Polo C et al. Clinical manifestations of intermediate allele carriers in Huntington disease. Neurology. 2016 Aug 9;87(6):571-578. https://doi.org/10.1212/WNL.0000000000002944
Cubo, Esther ; Ramos-Arroyo, María A. ; Martinez-Horta, Saul ; Martínez-Descalls, Asunción ; Calvo, Sara ; Gil-Polo, Cecilia ; European HD Network. / Clinical manifestations of intermediate allele carriers in Huntington disease. In: Neurology. 2016 ; Vol. 87, No. 6. pp. 571-578.
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abstract = "OBJECTIVE: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry.METHODS: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores.RESULTS: Of 12,190 participants, 657 (5.38{\%}) with <36 CAG repeats were identified: 76 IA carriers (11.56{\%}) and 581 controls (88.44{\%}). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p = 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p = 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p = 0.002).CONCLUSIONS: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling.CLINICALTRIALSGOV IDENTIFIER: NCT01590589.",
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T1 - Clinical manifestations of intermediate allele carriers in Huntington disease

AU - Cubo, Esther

AU - Ramos-Arroyo, María A.

AU - Martinez-Horta, Saul

AU - Martínez-Descalls, Asunción

AU - Calvo, Sara

AU - Gil-Polo, Cecilia

AU - European HD Network

N1 - © 2016 American Academy of Neurology.

PY - 2016/8/9

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N2 - OBJECTIVE: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry.METHODS: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores.RESULTS: Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p = 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p = 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p = 0.002).CONCLUSIONS: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling.CLINICALTRIALSGOV IDENTIFIER: NCT01590589.

AB - OBJECTIVE: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry.METHODS: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores.RESULTS: Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p = 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p = 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p = 0.002).CONCLUSIONS: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling.CLINICALTRIALSGOV IDENTIFIER: NCT01590589.

U2 - 10.1212/WNL.0000000000002944

DO - 10.1212/WNL.0000000000002944

M3 - Article

VL - 87

SP - 571

EP - 578

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 6

ER -