TY - JOUR
T1 - FXTAS is rare among Portuguese patients with movement disorders
T2 - FMR1 premutations may be associated with a wider spectrum of phenotypes
AU - Seixas, Ana I.
AU - Vale, José
AU - Jorge, Paula
AU - Marques, Isabel
AU - Santos, Rosário
AU - Alonso, Isabel
AU - Fortuna, Ana M.
AU - Pinto-Basto, Jorge
AU - Coutinho, Paula
AU - Margolis, Russell L.
AU - Sequeiros, Jorge
AU - Silveira, Isabel
N1 - Funding Information:
We would like to thank the patients and their families for participating in the study, and E. Cruz, A.M. Lopes, V. Mendes, and J. Cerqueira for technical assistance. This work was supported by research grant PIC/IC/82897/2007, FCT (Fundação para a Ciência e Tecnologia) and co-funded by FEDER. A.I.S. was the recipient of a scholarship from FCT (SFRH/BD/30702/2006). The experiments performed complied with the currently accepted ethical norms and national laws.
PY - 2011/6/3
Y1 - 2011/6/3
N2 - The fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by expansions of 55-200 CGG repeats in the 5'UTR of the FMR1 gene. These FMR1 premutation expansions have relatively high frequency in the general population. To estimate the frequency of FMR1 premutations among Portuguese males with non-familial, late-onset movement disorders of unknown etiology, we assessed CGG repeat size in males with disease onset after the age of 50 and negative or unknown family history for late-onset movement disorders, who were sent for SCA, HD, or PD genetic testing at a reference laboratory. The selected patients had a primary clinical diagnosis based on one of the following cardinal features of FXTAS: ataxia, tremor, or cognitive decline. A total of 86 subjects were genotyped for the CGG repeat in the FMR1 gene. We detected one patient with an expansion in the premutation range. The frequency of FMR1 premutations was 1.9% (1/54) in our group of patients with ataxia as the primary clinical feature, and 1.2% (1/86) in the larger movement disorders group. In the family of the FXTAS case, premutation-transmitting females presented a history of psychiatric symptoms, suggesting that, given the wide phenotypical expression of the premutation in females, neuropsychiatric surveillance is necessary. In conclusion, genetic testing for FXTAS should be made available to patients with adult-onset movement disorders to enable adequate genetic counseling to family members.
AB - The fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by expansions of 55-200 CGG repeats in the 5'UTR of the FMR1 gene. These FMR1 premutation expansions have relatively high frequency in the general population. To estimate the frequency of FMR1 premutations among Portuguese males with non-familial, late-onset movement disorders of unknown etiology, we assessed CGG repeat size in males with disease onset after the age of 50 and negative or unknown family history for late-onset movement disorders, who were sent for SCA, HD, or PD genetic testing at a reference laboratory. The selected patients had a primary clinical diagnosis based on one of the following cardinal features of FXTAS: ataxia, tremor, or cognitive decline. A total of 86 subjects were genotyped for the CGG repeat in the FMR1 gene. We detected one patient with an expansion in the premutation range. The frequency of FMR1 premutations was 1.9% (1/54) in our group of patients with ataxia as the primary clinical feature, and 1.2% (1/86) in the larger movement disorders group. In the family of the FXTAS case, premutation-transmitting females presented a history of psychiatric symptoms, suggesting that, given the wide phenotypical expression of the premutation in females, neuropsychiatric surveillance is necessary. In conclusion, genetic testing for FXTAS should be made available to patients with adult-onset movement disorders to enable adequate genetic counseling to family members.
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U2 - 10.1186/1744-9081-7-19
DO - 10.1186/1744-9081-7-19
M3 - Article
C2 - 21639881
AN - SCOPUS:79957829884
SN - 1744-9081
VL - 7
JO - Behavioral and Brain Functions
JF - Behavioral and Brain Functions
M1 - 19
ER -