Large CACNA1A deletion in a family with episodic ataxia type 2.
BACKGROUND
Episodic ataxia (EA) is an ion channel disorder that manifests as paroxysmal attacks of imbalance and incoordination. Episodic ataxia type 2 (EA2) is characterized by prolonged episodes of ataxia with interictal nystagmus and is caused by mutations in CACNA1A. All mutations identified thus far (to our knowledge) are nonsense or missense point mutations.


OBJECTIVE
To describe a family with EA2 having a novel mutation deleting several exons of CACNA1A.


METHODS
Clinical and molecular study of a family manifesting EA2 attacks.


METHODS
Academic research.


METHODS
DNA was extracted from blood samples of 3 family members.


METHODS
Microsatellite genotyping of CACNA1A, quantitative multiplex polymerase chain reaction of short fluorescent fragments (QMPSF), and sequencing were performed.


RESULTS
Genotyping of CACNA1A showed nonmendelian inheritance of a CAG repeat located at the 3' end of the gene in a mother and daughter, suggesting a deletion event, which was subsequently confirmed by QMPSF analysis and sequencing. This 39.5-kilobase deletion removes the last 16 coding exons of the gene.


CONCLUSIONS
Deletion of several exons of CACNA1A may cause EA2 and should be assessed in patients having EA2 without a CACNA1A point mutation.
Riant
Florence
F
Laboratoire de Génétique, Groupe Hospitalier Lariboisière-Fernand Widal, Groupement Hospitalier-Universitaire Nord, Assistance Publique-Hôpitaux de Paris, 2 Rue Ambroise Paré, 75010 Paris, France. florence.riant@lrb.aphp.fr
Mourtada
Reda
R
Saugier-Veber
Pascale
P
Tournier-Lasserve
Elisabeth
E
D024509:3' Flanking Region / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015220:Calcium Channels / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000145:classification* / Q000235:genetics*; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type