A novel ferritin light chain gene mutation in a Japanese family with neuroferritinopathy: description of clinical features and implications for genotype-phenotype correlations.
Neuroferritinopathy is a hereditary neurodegenerative disorder caused by mutations in the ferritin light chain gene (FTL1). The cardinal features are progressive movement disturbance, hypoferritinemia, and iron deposition in the brain. To date, five mutations have been described in Caucasian and Japanese families, but the genotype-phenotype correlations remain to be established. We identified a novel FTL1 mutation (exon 4, c.641/642, 4-nucletotide duplication) in a Japanese family and compared the clinical traits with those previously reported. All mutations but one are insertions in exon 4, resulting in frameshifts. Clinical features are similar among patients with the same mutations. Middle-age onset chorea is common in patients with insertions in the 5' portion of exon 4 including our cases, whereas patients with insertions in the 3' portion of exon 4 develop early-onset tremor, suggesting genotype-phenotype correlations. In this family, male predominance and normal serum ferritin levels are characteristic.
Kubota
Akatsuki
A
Department of Neurology, The University of Tokyo, Tokyo, Japan.
Hida
Ayumi
A
Ichikawa
Yaeko
Y
Momose
Yoshio
Y
Goto
Jun
J
Igeta
Yukifusa
Y
Hashida
Hideji
H
Yoshida
Kunihiro
K
Ikeda
Syu-Ichi
S
Kanazawa
Ichiro
I
Tsuji
Shoji
S
D000328:Adult; D001052:Apoferritins / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005091:Exons; D005293:Ferritins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009069:Movement Disorders / Q000235:genetics* / Q000503:physiopathology*; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D012720:Severity of Illness Index
D005293:Ferritins; D001052:Apoferritins