PRRT2-related disorders: further PKD and ICCA cases and review of the literature.
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PRRT2-related disorders: further PKD and ICCA cases and review of the literature. / Becker, Felicitas; Schubert, Julian; Striano, Pasquale; Anttonen, Anna-Kaisa; Liukkonen, Elina; Gaily, Eija; Gerloff, Christian; Müller, Stephan; Heußinger, Nicole; Kellinghaus, Christoph; Robbiano, Angela; Polvi, Anne; Zittel, Simone; Oertzen, von; Tim, J; Rostasy, Kevin; Schöls, Ludger; Warner, Tom; Münchau, Alexander; Lehesjoki, Anna-Elina; Zara, Federico; Lerche, Holger; Weber, Yvonne G.
in: J NEUROL, Jahrgang 260, Nr. 5, 5, 2013, S. 1234-1244.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - PRRT2-related disorders: further PKD and ICCA cases and review of the literature.
AU - Becker, Felicitas
AU - Schubert, Julian
AU - Striano, Pasquale
AU - Anttonen, Anna-Kaisa
AU - Liukkonen, Elina
AU - Gaily, Eija
AU - Gerloff, Christian
AU - Müller, Stephan
AU - Heußinger, Nicole
AU - Kellinghaus, Christoph
AU - Robbiano, Angela
AU - Polvi, Anne
AU - Zittel, Simone
AU - Oertzen, von
AU - Tim, J
AU - Rostasy, Kevin
AU - Schöls, Ludger
AU - Warner, Tom
AU - Münchau, Alexander
AU - Lehesjoki, Anna-Elina
AU - Zara, Federico
AU - Lerche, Holger
AU - Weber, Yvonne G
PY - 2013
Y1 - 2013
N2 - Recent studies reported mutations in the gene encoding the proline-rich transmembrane protein 2 (PRRT2) to be causative for paroxysmal kinesigenic dyskinesia (PKD), PKD combined with infantile seizures (ICCA), and benign familial infantile seizures (BFIS). PRRT2 is a presynaptic protein which seems to play an important role in exocytosis and neurotransmitter release. PKD is the most common form of paroxysmal movement disorder characterized by recurrent brief involuntary hyperkinesias triggered by sudden movements. Here, we sequenced PRRT2 in 14 sporadic and 8 familial PKD and ICCA cases of Caucasian origin and identified three novel mutations (c.919C>T/p.Gln307, c.388delG/p.Ala130Profs 46, c.884G>A/p.Arg295Gln) predicting two truncated proteins and one probably damaging point mutation. A review of all published cases is also included. PRRT2 mutations occur more frequently in familial forms of PRRT2-related syndromes (80-100 %) than in sporadic cases (33-46 %) suggesting further heterogeneity in the latter. PRRT2 mutations were rarely described in other forms of paroxysmal dyskinesias deviating from classical PKD, as we report here in one ICCA family without kinesigenic triggers. Mutations are exclusively found in two exons of the PRRT2 gene at a high rate across all syndromes and with one major mutation (c.649dupC) in a mutational hotspot of nine cytosines, which is responsible for 57 % of all cases in all phenotypes. We therefore propose that genetic analysis rapidly performed in early stages of the disease is highly cost-effective and can help to avoid further unnecessary diagnostic and therapeutic interventions.
AB - Recent studies reported mutations in the gene encoding the proline-rich transmembrane protein 2 (PRRT2) to be causative for paroxysmal kinesigenic dyskinesia (PKD), PKD combined with infantile seizures (ICCA), and benign familial infantile seizures (BFIS). PRRT2 is a presynaptic protein which seems to play an important role in exocytosis and neurotransmitter release. PKD is the most common form of paroxysmal movement disorder characterized by recurrent brief involuntary hyperkinesias triggered by sudden movements. Here, we sequenced PRRT2 in 14 sporadic and 8 familial PKD and ICCA cases of Caucasian origin and identified three novel mutations (c.919C>T/p.Gln307, c.388delG/p.Ala130Profs 46, c.884G>A/p.Arg295Gln) predicting two truncated proteins and one probably damaging point mutation. A review of all published cases is also included. PRRT2 mutations occur more frequently in familial forms of PRRT2-related syndromes (80-100 %) than in sporadic cases (33-46 %) suggesting further heterogeneity in the latter. PRRT2 mutations were rarely described in other forms of paroxysmal dyskinesias deviating from classical PKD, as we report here in one ICCA family without kinesigenic triggers. Mutations are exclusively found in two exons of the PRRT2 gene at a high rate across all syndromes and with one major mutation (c.649dupC) in a mutational hotspot of nine cytosines, which is responsible for 57 % of all cases in all phenotypes. We therefore propose that genetic analysis rapidly performed in early stages of the disease is highly cost-effective and can help to avoid further unnecessary diagnostic and therapeutic interventions.
M3 - SCORING: Journal article
VL - 260
SP - 1234
EP - 1244
JO - J NEUROL
JF - J NEUROL
SN - 0340-5354
IS - 5
M1 - 5
ER -
