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Novel mutations consolidate KCTD7 as a progressive myoclonus epilepsy gene

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Novel mutations consolidate KCTD7 as a progressive myoclonus epilepsy gene. / Kousi, Maria; Anttila, Verneri; Schulz, Angela; Calafato, Stella; Jakkula, Eveliina; Riesch, Erik; Myllykangas, Liisa; Kalimo, Hannu; Topçu, Meral; Gökben, Sarenur; Alehan, Fusun; Lemke, Johannes R; Alber, Michael; Palotie, Aarno; Kopra, Outi; Lehesjoki, Anna-Elina.

in: J MED GENET, Jahrgang 49, Nr. 6, 01.06.2012, S. 391-9.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Kousi, M, Anttila, V, Schulz, A, Calafato, S, Jakkula, E, Riesch, E, Myllykangas, L, Kalimo, H, Topçu, M, Gökben, S, Alehan, F, Lemke, JR, Alber, M, Palotie, A, Kopra, O & Lehesjoki, A-E 2012, 'Novel mutations consolidate KCTD7 as a progressive myoclonus epilepsy gene', J MED GENET, Jg. 49, Nr. 6, S. 391-9. https://doi.org/10.1136/jmedgenet-2012-100859

APA

Kousi, M., Anttila, V., Schulz, A., Calafato, S., Jakkula, E., Riesch, E., Myllykangas, L., Kalimo, H., Topçu, M., Gökben, S., Alehan, F., Lemke, J. R., Alber, M., Palotie, A., Kopra, O., & Lehesjoki, A-E. (2012). Novel mutations consolidate KCTD7 as a progressive myoclonus epilepsy gene. J MED GENET, 49(6), 391-9. https://doi.org/10.1136/jmedgenet-2012-100859

Vancouver

Kousi M, Anttila V, Schulz A, Calafato S, Jakkula E, Riesch E et al. Novel mutations consolidate KCTD7 as a progressive myoclonus epilepsy gene. J MED GENET. 2012 Jun 1;49(6):391-9. https://doi.org/10.1136/jmedgenet-2012-100859

Bibtex

@article{f037b64c1c80487d8688cb20d7fd269b,
title = "Novel mutations consolidate KCTD7 as a progressive myoclonus epilepsy gene",
abstract = "BACKGROUND: The progressive myoclonus epilepsies (PMEs) comprise a group of clinically and genetically heterogeneous disorders characterised by myoclonus, epilepsy, and neurological deterioration. This study aimed to identify the underlying gene(s) in childhood onset PME patients with unknown molecular genetic background.METHODS: Homozygosity mapping was applied on genome-wide single nucleotide polymorphism data of 18 Turkish patients. The potassium channel tetramerisation domain-containing 7 (KCTD7) gene, previously associated with PME in a single inbred family, was screened for mutations. The spatiotemporal expression of KCTD7 was assessed in cellular cultures and mouse brain tissue.RESULTS: Overlapping homozygosity in 8/18 patients defined a 1.5 Mb segment on 7q11.21 as the major candidate locus. Screening of the positional candidate gene KCTD7 revealed homozygous missense mutations in two of the eight cases. Screening of KCTD7 in a further 132 PME patients revealed four additional mutations (two missense, one in-frame deletion, and one frameshift-causing) in five families. Eight patients presented with myoclonus and epilepsy and one with ataxia, the mean age of onset being 19 months. Within 2 years after onset, progressive loss of mental and motor skills ensued leading to severe dementia and motor handicap. KCTD7 showed cytosolic localisation and predominant neuronal expression, with widespread expression throughout the brain. None of three polypeptides carrying patient missense mutations affected the subcellular distribution of KCTD7.DISCUSSION: These data confirm the causality of KCTD7 defects in PME, and imply that KCTD7 mutation screening should be considered in PME patients with onset around 2 years of age followed by rapid mental and motor deterioration.",
keywords = "Animals, Blotting, Western, Brain Chemistry, Cells, Cultured, Chromosome Mapping, Homozygote, Humans, Intracellular Space, Mice, Microscopy, Fluorescence, Mutation, Myoclonic Epilepsies, Progressive, Pedigree, Phenotype, Polymorphism, Single Nucleotide, Potassium Channels, Sequence Analysis, DNA, Turkey",
author = "Maria Kousi and Verneri Anttila and Angela Schulz and Stella Calafato and Eveliina Jakkula and Erik Riesch and Liisa Myllykangas and Hannu Kalimo and Meral Top{\c c}u and Sarenur G{\"o}kben and Fusun Alehan and Lemke, {Johannes R} and Michael Alber and Aarno Palotie and Outi Kopra and Anna-Elina Lehesjoki",
year = "2012",
month = jun,
day = "1",
doi = "10.1136/jmedgenet-2012-100859",
language = "English",
volume = "49",
pages = "391--9",
journal = "J MED GENET",
issn = "0022-2593",
publisher = "BMJ PUBLISHING GROUP",
number = "6",

}

RIS

TY - JOUR

T1 - Novel mutations consolidate KCTD7 as a progressive myoclonus epilepsy gene

AU - Kousi, Maria

AU - Anttila, Verneri

AU - Schulz, Angela

AU - Calafato, Stella

AU - Jakkula, Eveliina

AU - Riesch, Erik

AU - Myllykangas, Liisa

AU - Kalimo, Hannu

AU - Topçu, Meral

AU - Gökben, Sarenur

AU - Alehan, Fusun

AU - Lemke, Johannes R

AU - Alber, Michael

AU - Palotie, Aarno

AU - Kopra, Outi

AU - Lehesjoki, Anna-Elina

PY - 2012/6/1

Y1 - 2012/6/1

N2 - BACKGROUND: The progressive myoclonus epilepsies (PMEs) comprise a group of clinically and genetically heterogeneous disorders characterised by myoclonus, epilepsy, and neurological deterioration. This study aimed to identify the underlying gene(s) in childhood onset PME patients with unknown molecular genetic background.METHODS: Homozygosity mapping was applied on genome-wide single nucleotide polymorphism data of 18 Turkish patients. The potassium channel tetramerisation domain-containing 7 (KCTD7) gene, previously associated with PME in a single inbred family, was screened for mutations. The spatiotemporal expression of KCTD7 was assessed in cellular cultures and mouse brain tissue.RESULTS: Overlapping homozygosity in 8/18 patients defined a 1.5 Mb segment on 7q11.21 as the major candidate locus. Screening of the positional candidate gene KCTD7 revealed homozygous missense mutations in two of the eight cases. Screening of KCTD7 in a further 132 PME patients revealed four additional mutations (two missense, one in-frame deletion, and one frameshift-causing) in five families. Eight patients presented with myoclonus and epilepsy and one with ataxia, the mean age of onset being 19 months. Within 2 years after onset, progressive loss of mental and motor skills ensued leading to severe dementia and motor handicap. KCTD7 showed cytosolic localisation and predominant neuronal expression, with widespread expression throughout the brain. None of three polypeptides carrying patient missense mutations affected the subcellular distribution of KCTD7.DISCUSSION: These data confirm the causality of KCTD7 defects in PME, and imply that KCTD7 mutation screening should be considered in PME patients with onset around 2 years of age followed by rapid mental and motor deterioration.

AB - BACKGROUND: The progressive myoclonus epilepsies (PMEs) comprise a group of clinically and genetically heterogeneous disorders characterised by myoclonus, epilepsy, and neurological deterioration. This study aimed to identify the underlying gene(s) in childhood onset PME patients with unknown molecular genetic background.METHODS: Homozygosity mapping was applied on genome-wide single nucleotide polymorphism data of 18 Turkish patients. The potassium channel tetramerisation domain-containing 7 (KCTD7) gene, previously associated with PME in a single inbred family, was screened for mutations. The spatiotemporal expression of KCTD7 was assessed in cellular cultures and mouse brain tissue.RESULTS: Overlapping homozygosity in 8/18 patients defined a 1.5 Mb segment on 7q11.21 as the major candidate locus. Screening of the positional candidate gene KCTD7 revealed homozygous missense mutations in two of the eight cases. Screening of KCTD7 in a further 132 PME patients revealed four additional mutations (two missense, one in-frame deletion, and one frameshift-causing) in five families. Eight patients presented with myoclonus and epilepsy and one with ataxia, the mean age of onset being 19 months. Within 2 years after onset, progressive loss of mental and motor skills ensued leading to severe dementia and motor handicap. KCTD7 showed cytosolic localisation and predominant neuronal expression, with widespread expression throughout the brain. None of three polypeptides carrying patient missense mutations affected the subcellular distribution of KCTD7.DISCUSSION: These data confirm the causality of KCTD7 defects in PME, and imply that KCTD7 mutation screening should be considered in PME patients with onset around 2 years of age followed by rapid mental and motor deterioration.

KW - Animals

KW - Blotting, Western

KW - Brain Chemistry

KW - Cells, Cultured

KW - Chromosome Mapping

KW - Homozygote

KW - Humans

KW - Intracellular Space

KW - Mice

KW - Microscopy, Fluorescence

KW - Mutation

KW - Myoclonic Epilepsies, Progressive

KW - Pedigree

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Potassium Channels

KW - Sequence Analysis, DNA

KW - Turkey

U2 - 10.1136/jmedgenet-2012-100859

DO - 10.1136/jmedgenet-2012-100859

M3 - SCORING: Journal article

C2 - 22693283

VL - 49

SP - 391

EP - 399

JO - J MED GENET

JF - J MED GENET

SN - 0022-2593

IS - 6

ER -