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Analysis of the C 9orf72 Gene in Patients with Amyotrophic Lateral Sclerosis in Spain and Different Populations Worldwide
Author(s) -
GarcíaRedondo Alberto,
DolsIcardo Oriol,
RojasGarcía Ricard,
EstebanPérez Jesús,
CorderoVázquez Pilar,
MuñozBlanco José Luis,
Catalina Irene,
GonzálezMuñoz Miguel,
Varona Luis,
Sarasola Esther,
Povedano Monica,
Sevilla Teresa,
Guerrero Antonio,
Pardo Julio,
de Munain Adolfo López,
MárquezInfante Celedonio,
de Rivera Francisco Javier Rodríguez,
Pastor Pau,
Jericó Ivonne,
de Arcaya Amaya Álvarez,
Mora Jesús S.,
Clarimón Jordi,
GonzaloMartínez Juan Francisco,
JuárezRufián Alexandra,
Atencia Gabriela,
JiménezBautista Rosario,
Morán Yolanda,
Mascías Javier,
HernándezBarral María,
Kapetanovic Solange,
GarcíaBarcina María,
Alcalá Carmen,
Vela Álvaro,
RamírezRamos Concepción,
Galán Lucía,
PérezTur Jordi,
Quintáns Beatriz,
Sobrido M Jesús,
FernándezTorrón Roberto,
Poza Juan José,
Gorostidi Ana,
Paradas Carmen,
Villoslada Pablo,
Larrodé Pilar,
Capablo José Luis,
PascualCalvet Jordi,
Goñi Miguel,
Morgado Yolanda,
Guitart Miriam,
MorenoLaguna Sira,
Rueda Almudena,
MartínEstefanía Carlos,
Cemillán Carlos,
Blesa Rafael,
Lleó Alberto
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22211
Subject(s) - c9orf72 , amyotrophic lateral sclerosis , haplotype , frontotemporal dementia , biology , genetics , allele , trinucleotide repeat expansion , mutation , family history , founder effect , dementia , gene , disease , medicine
A hexanucleotide repeat expansion in chromosome 9 open reading frame 72 ( C 9orf72 ) can cause amyotrophic lateral sclerosis ( ALS ) and/or frontotemporal dementia ( FTD ). We assessed its frequency in 781 sporadic ALS (s ALS ) and 155 familial ALS (f ALS ) cases, and in 248 S panish controls. We tested the presence of the reported founder haplotype among mutation carriers and in 171 C eph E uropeans from U tah ( CEU ), 170 Y oruba A fricans, 81 H an C hinese, and 85 J apanese subjects. The C 9orf72 expansion was present in 27.1% of f ALS and 3.2% of s ALS . Mutation carriers showed lower age at onset ( P = 0.04), shorter survival ( P = 0.02), greater co‐occurrence of FTD ( P = 8.2 × 10 −5 ), and more family history of ALS ( P = 1.4 × 10 −20 ), than noncarriers. No association between alleles within the normal range and the risk of ALS was found ( P = 0.12). All 61 of the mutation carriers were tested and a patient carrying 28 hexanucleotide repeats presented with the founder haplotype. This haplotype was found in 5.6% Y oruba A fricans, 8.9% CEU , 3.9% J apanese, and 1.6% H an C hinese chromosomes.