KCTD7 (7q11.21), CLN14,EPN3.

 https://www.ncbi.nlm.nih.gov/gene/154881

Epileptic Disord. 2016 Sep 1;18(S2):115-119.

KCTD7-related progressive myoclonus epilepsy.

Van Bogaert P¹.

Progressive myoclonic epilepsy associated with KCTD7 mutations has been reported in 19 patients from 12 families. Patients show homozygous mutations in the coding regions of the KCTD7 gene. The disease starts in infancy. Patients typically show an initial severe epileptic disorder, with abundant epileptiform discharges on EEG and myoclonic seizures in the foreground, associated with cognitive regression and ataxia. Continuous multifocal myoclonus aggravated by action is observed in more than half of the cases. After a few years, the disease tends to stabilize and long survival can be expected. Some patients remain able to walk independently. The severity of the disease is variable from one patient to another, even within the same family. It is hypothesized that the epileptic disorder may influence the neurological regression observed in patients.KEYWORDS:

KCTD7; encephalopathy; infancy; progressive myoclonus epilepsiesPMID:

27629772DOI:10.1684/epd.2016.0856

Related articles in PubMed

1. KCTD7-related progressive myoclonus epilepsy. Van Bogaert P. Epileptic Disord, 2016 Sep 1. PMID 27629772
2. Linkage analysis and exome sequencing identify a novel mutation in KCTD7 in patients with progressive myoclonus epilepsy with ataxia. Farhan SM, et al. Epilepsia, 2014 Sep. PMID 25060828
3. Novel mutations consolidate KCTD7 as a progressive myoclonus epilepsy gene. Kousi M, et al. J Med Genet, 2012 Jun. PMID 22693283, Free PMC Article
4. Novel mutation in potassium channel related gene KCTD7 and progressive myoclonic epilepsy. Krabichler B, et al. Ann Hum Genet, 2012 Jul. PMID 22606975
5. Mutation of a potassium channel-related gene in progressive myoclonic epilepsy. Van Bogaert P, et al. Ann Neurol, 2007 Jun. PMID 17455289

See all (26) citations in PubMed

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

1. Biallelic KCTD7 mutations define a neurodegenerative disorder with lipofuscin and lipid droplet accumulation but without defining features of neuronal ceroid lipofuscinosis or lysosomal storage disorders
2. KCTD7 has an impact on K+ fluxes, neurotransmitter synthesis and neuronal function, and that malfunction of the encoded protein may lead to progressive myoclonus epilepsy.Abstract
   Progressive myoclonus epilepsy is a heterogeneous group of disorders characterized by myoclonic and tonic-clonic seizures, ataxia and cognitive decline. We here present two affected brothers. At 9 months of age the elder brother developed ataxia and myoclonic jerks. In his second year he lost the ability to walk and talk, and he developed drug-resistant progressive myoclonus epilepsy. The cerebrospinal fluid level of glutamate was decreased while glutamine was increased. His younger brother manifested similar symptoms from 6 months of age. By exome sequencing of the proband we identified a novel homozygous frameshift variant in the potassium channel tetramerization domain 7 (KCTD7) gene (NM_153033.1:c.696delT: p.F232fs), which results in a truncated protein. The identified F232fs variant is inherited in an autosomal recessive manner, and the healthy consanguineous parents carry the variant in a heterozygous state. Bioinformatic analyses and structure modelling showed that KCTD7 is a highly conserved protein, structurally similar to KCTD5 and several voltage-gated potassium channels, and that it may form homo- or heteromultimers. By heterologous expression in Xenopus laevis oocytes, we demonstrate that wild-type KCTD7 hyperpolarizes cells in a K⁺ dependent manner and regulates activity of the neuronal glutamine transporter SAT2 (Slc38a2), while the F232fs variant impairs K⁺ fluxes and obliterates SAT2-dependent glutamine transport. Characterization of four additional disease-causing variants (R94W, R184C, N273I, Y276C) bolster these results and reveal the molecular mechanisms involved in the pathophysiology of KCTD7-related progressive myoclonus epilepsy. Thus, our data demonstrate that KCTD7 has an impact on K⁺ fluxes, neurotransmitter synthesis and neuronal function, and that malfunction of the encoded protein may lead to progressive myoclonus epilepsy.
   

   © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.KEYWORDS:
   BTB/POZ domain; KCTD7; Kv channel; PME; Slc38
3. reviews the phenotype of progressive myoclonic epilepsy associated with KCTD7 mutations [review]
4. This study identified that novel KCTD7 mutation in patients with progressive myoclonus epilepsy with ataxia.
5. The KCTD7 gene, previously associated with progressive myoclonus epilepsies (PMEs) in a single inbred family, was screened for mutations in 18 Turkish PME patients.
6. this study clearly demonstrates that KCTD7 mutations also cause a rare, infantile-onset NCL subtype designated as CLN14.
7. We found a C to T mutation in exon 2 of the potassium channel tetramerization domain containing 7 gene(KCTD7)in a progressive myoclonic epilepsy family affecting a highly conserved segment of the predicted protein changing an arginine codon to a stop.