A hexanucleotide repeat expansion in C9ORF72 causes familial and sporadic ALS in Taiwan.
A GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene was recently identified as an important cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in Caucasian populations. The role of the C9ORF72 repeat expansion in ALS in Chinese populations has received little attention. We therefore performed mutation analyses in a Taiwanese cohort of 22 unrelated familial ALS (FALS) patients and 102 sporadic ALS patients of Han Chinese descent. The C9ORF72 mutation was found in 4 FALS (18.2%; 4/22) and 2 sporadic ALS patients (2.0%; 2/102). The C9ORF72 repeat numbers in the 300 healthy controls and the 118 ALS patients without the C9ORF72 mutation ranged from 3 to 15. Needle biopsy in the left frontal cortex of 1 patient with FALS-frontotemporal dementia revealed numerous cytoplasmic TAR DNA-binding protein 43 (TDP-43) inclusions and minimal neuritis, consistent with type B frontotemporal lobar degeneration with TDP-43 (FTLD-TDP) pathology. This study clearly demonstrates the existence and importance of the C9ORF72 hexanucleotide repeat expansion in a Taiwanese ALS cohort of Chinese origin, and supports the global presence of the C9ORF72 repeat expansion in ALS.
Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.
Ching-Paio
CP
Tsai
Bing-Wen
BW
Soong
Pang-Hsien
PH
Tu
Kon-Ping
KP
Lin
Jong-Ling
JL
Fuh
Pei-Chien
PC
Tsai
Yi-Chun
YC
Lu
I-Hui
IH
Lee
Yi-Chung
YC
Lee
D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000473:pathology; D000073885:C9orf72 Protein; D004252:DNA Mutational Analysis; D042622:DNA Repeat Expansion / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000235:genetics*; D013624:Taiwan / Q000453:epidemiology; D025801:Ubiquitin / Q000378:metabolism
D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins; D025801:Ubiquitin