Possible anticipation associated with a novel splice site mutation in episodic ataxia type 2.
Anticipation is a phenomenon characterized by decreasing age at onset and increasing severity of symptoms of a disease in successive generations within a pedigree. Anticipation mostly occurs in neurodegenerative diseases with expansion of unstable trinucleotide repeats. However, it has not been previously pointed out in episodic ataxia type 2 (EA2). Clinical and genetic analyses were performed in nine members from three consecutive generations of a Korean family with EA2. We performed a polymerase chain reaction (PCR)-based direct sequence analysis of all coding regions of CACNA1A using genomic DNA. The clinically affected family members showed recurrent vertigo, interictal nystagmus, and childhood epilepsy. There is a decrease in the age onset (possible genetic anticipation) in three succeeding generations of the family. Genetic analysis identified a splice site mutation (p.Val1465Glyfs13X) and normal trinucleotide repeats in CACNA1A in all clinically affected and one unaffected members. Recognizing anticipation would aid in genetic counseling in EA2.
Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Biomedical Research Institute, Pusan, Korea.
Kwang-Dong
KD
Choi
Ji-Won
JW
Yook
Min-Ji
MJ
Kim
Hyang-Sook
HS
Kim
Young-Eun
YE
Park
Ji Soo
JS
Kim
Jae-Hwan
JH
Choi
Jin-Hong
JH
Shin
Dae-Seong
DS
Kim
D017668:Age of Onset; D000368:Aged; D020132:Anticipation, Genetic / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001259:Ataxia / Q000235:genetics*; D015220:Calcium Channels / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009759:Nystagmus, Pathologic / Q000235:genetics*; D010375:Pedigree; D022821:RNA Splice Sites; D018911:Trinucleotide Repeats / Q000235:genetics; D055815:Young Adult; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; D022821:RNA Splice Sites; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type