Clinical phenotypes of a large Chinese multigenerational kindred with autosomal dominant familial ALS due to Ile149Thr SOD1 gene mutation.
About 10% of amyotrophic lateral sclerosis (ALS) cases are familial. We identified a five-generation Chinese family with autosomal dominant familial ALS (FALS). We performed a detailed family study, clinical and electromyographic validation, and SOD1, VEGF and CNTF mutation analyses. Forty-five living members (16 affected) were studied and DNA samples collected. Genealogical data were collected for deceased members. Based on the duration between symptom onset to ventilator dependence, they were divided into rapidly progressive (range 1-18 months, mean (SD) duration = 12.08 (+/-6.10) months, mean (SD) age of symptom onset = 39.75 (+/-9.84) years) and slowly progressive groups (>18 months; mean (SD) age of onset = 37.25 (+/-5.32) years old). We identified a heterozygous mutation of ATT to ACT of SOD1 gene at codon 149 in exon 5 resulting in substitution of isoleucine to threonine. It co-segregated with all affected members and 11 non-symptomatic members. We report a large multigenerational Chinese FALS kindred with I149T mutation in SOD1. No polymorphisms or mutations were found to date in two known modifier genes, namely, VEGF and CNTF, which were associated with heterogeneity in the phenotype within this kindred. Follow-up of the family will be helpful to explore any potential disease markers.
Fong
Gardian C Y
GC
Division of Neurology, University Department of Medicine, University of Hong Kong, Hong Kong.
Kwok
Ken H H
KH
Song
Y Q
YQ
Cheng
T S
TS
Ho
Philip W L
PW
Chu
Andrew C Y
AC
Kung
Michelle H W
MH
Chan
K H
KH
Mak
Windsor
W
Cheung
Raymond T F
RT
Ramsden
David B
DB
Ho
S L
SL
D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D044466:Asian People; D020934:Ciliary Neurotrophic Factor / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D006801:Humans; D007532:Isoleucine / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D013912:Threonine / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D020934:Ciliary Neurotrophic Factor; C000606290:SOD1 protein, human; D042461:Vascular Endothelial Growth Factor A; D007532:Isoleucine; D013912:Threonine; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1