Atypical pyridoxine-dependent epilepsy due to a pseudoexon in ALDH7A1.
We report two siblings with atypical pyridoxine-dependant epilepsy, modest elevation of biomarkers, in which the open reading frame and the splice sites of ALDH7A1 did not show any mutations. Subsequent genetic analysis revealed a deep homozygous intronic mutation in ALDH7A1 resulting in two types of transcripts: the major transcript containing a pseudoexon, and the minor transcript representing the authentic spliced transcript. In future, this mutation may be targeted with antisense-therapy aiming at exclusion of the pseudoexon.
INSERM, U910, Aix-Marseille Université, Marseille, France. mathieu.milh@ap-hm.fr
Mathieu
M
Milh
Ana
A
Pop
Warsha
W
Kanhai
Nathalie
N
Villeneuve
Aline
A
Cano
Eduard A
EA
Struys
Gajja S
GS
Salomons
Brigitte
B
Chabrol
Cornelis
C
Jakobs
D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007438:Introns / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D035781:Siblings
C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase