TY - JOUR
T1 - Role of mitochondrial DNA variants in the development of fragile X-associated tremor/ataxia syndrome
AU - Alvarez-Mora, Maria Isabel
AU - Santos, Cristina
AU - Carreño-Gago, Lidia
AU - Madrigal, Irene
AU - Tejada, Maria Isabel
AU - Martinez, Francisco
AU - Izquierdo-Alvarez, Silvia
AU - Garcia-Arumi, Elena
AU - Mila, Montserrat
AU - Rodriguez-Revenga, Laia
N1 - Funding Information:
This work was supported by the Instituto de Salud Carlos III ( PI12/00879 and PI17/01067 ), co-financed by Fondo Europeo de Desarrollo Regional (FEDER) “una manera de hacer Europa” and AGAUR from the Autonomous Catalan Government ( 2014 SGR603 ; 2014 SGR1420 ; 2017 SGR1134 ). The CIBER de Enfermedades Raras is an initiative of the Instituto de Salud Carlos III.
Publisher Copyright:
© 2020
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/5
Y1 - 2020/5
N2 - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that appears in at least one-third of adult carriers of FMR1 premutation. Several studies have shown that mitochondrial dysfunction may play a role in neurodegenerative disorders. In order to assess whether mitochondrial DNA variants are involved in the risk of developing FXTAS we evaluated the frequency of mitochondrial haplogroups in 132 unrelated Spanish FMR1 premutation carriers. In addition, the entire mitogenome of 26 FMR1 premutation carriers was sequenced using massively parallel sequencing technologies to analyze mitochondrial DNA variants. Statistical analyses reveal a significant difference in the frequency of T haplogroup. Data analysis of mitochondrial DNA sequences evidence an association between FXTAS and the burden of heteroplasmic variants as well as their distribution. Our results suggest that haplogroup T might be a potential protective factor for FXTAS and that FXTAS individuals accumulate higher rates of heteroplasmic variants in compromised regions of the mitochondrial genome. These results may explain, in part, the role of mitochondrial DNA in the development of FXTAS.
AB - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that appears in at least one-third of adult carriers of FMR1 premutation. Several studies have shown that mitochondrial dysfunction may play a role in neurodegenerative disorders. In order to assess whether mitochondrial DNA variants are involved in the risk of developing FXTAS we evaluated the frequency of mitochondrial haplogroups in 132 unrelated Spanish FMR1 premutation carriers. In addition, the entire mitogenome of 26 FMR1 premutation carriers was sequenced using massively parallel sequencing technologies to analyze mitochondrial DNA variants. Statistical analyses reveal a significant difference in the frequency of T haplogroup. Data analysis of mitochondrial DNA sequences evidence an association between FXTAS and the burden of heteroplasmic variants as well as their distribution. Our results suggest that haplogroup T might be a potential protective factor for FXTAS and that FXTAS individuals accumulate higher rates of heteroplasmic variants in compromised regions of the mitochondrial genome. These results may explain, in part, the role of mitochondrial DNA in the development of FXTAS.
KW - FMR1 premutation
KW - FXTAS
KW - Low-level heteroplasmic variants
KW - Mitogenome
KW - mtDNA haplogroups
KW - Risk factors
UR - http://www.scopus.com/inward/record.url?scp=85082416811&partnerID=8YFLogxK
U2 - 10.1016/j.mito.2020.03.004
DO - 10.1016/j.mito.2020.03.004
M3 - Article
C2 - 32173566
AN - SCOPUS:85082416811
VL - 52
SP - 157
EP - 162
JO - Mitochondrion
JF - Mitochondrion
SN - 1567-7249
ER -