CHRNA2 and Nocturnal Frontal Lobe Epilepsy: Identification and Characterization of a Novel Loss of Function Mutation

Frontiers in Molecular Neuroscience
Chiara VillaRomina Combi

Abstract

Mutations in genes coding for subunits of the neuronal nicotinic acetylcholine receptor (nAChR) have been involved in familial sleep-related hypermotor epilepsy (also named autosomal dominant nocturnal frontal lobe epilepsy, ADNFLE). Most of these mutations reside in CHRNA4 and CHRNB2 genes, coding for the α4 and β2 nAChR subunits, respectively. Two mutations with contrasting functional effects were also identified in the CHRNA2 gene coding for the α2 subunit. Here, we report the third mutation in the CHRNA2, found in a patient showing ADNFLE. The patient was examined by scalp EEG, contrast-enhanced brain magnetic resonance imaging (MRI), and nocturnal video-polysomnographic recording. All exons and the exon-intron boundaries of CHRNA2, CHRNA4, CHRNB2, CRH, KCNT1 were amplified and Sanger sequenced. In the proband, we found a c.754T>C (p.Tyr252His) missense mutation located in the N-terminal ligand-binding domain and inherited from the mother. Functional studies were performed by transient co-expression of α2 and α2 Tyr252His , with either β2 or β4, in human embryonic kidney (HEK293) cells. Equimolar amounts of subunits expression were obtained by using F2A-based multi-cistronic constructs encoding for the genes relative to the...Continue Reading

References

Aug 15, 2000·The Journal of Comparative Neurology·M QuikJ W Langston
Oct 13, 2000·The European Journal of Neuroscience·Z Y HanJ P Changeux
Feb 18, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Evelyn K LambeGeorge K Aghajanian
Sep 27, 2005·Brain Research Bulletin·Romina CombiMaria Luisa Tenchini
Oct 3, 2006·Annual Review of Pharmacology and Toxicology·John A Dani, Daniel Bertrand
May 18, 2011·Biochemical Pharmacology·Christopher G Baddick, Michael J Marks
Nov 2, 2012·The Neurologist·Luigi Ferini-StrambiRomina Combi
Apr 2, 2013·Nature Genetics·Saeko IshidaStéphanie Baulac
Jul 26, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Francesca MazzoSara Francesca Colombo
Jan 8, 2014·Current Neurology and Neuroscience Reports·Lino NobiliPaolo Tinuper
Dec 3, 2014·Neuropharmacology·Michele ZoliCecilia Gotti
Feb 27, 2015·Frontiers in Physiology·Andrea BecchettiAlida Amadeo
May 11, 2016·Neurology·Paolo TinuperRuth Ottman
Aug 6, 2016·Proceedings of the National Academy of Sciences of the United States of America·Nikolaos KouvatsosSocrates J Tzartos
Oct 21, 2016·Nature·Claudio L Morales-PerezRyan E Hibbs

❮ Previous
Next ❯

Citations

Apr 23, 2020·Molecular Medicine Reports·Noemí Cárdenas-RodríguezIván Ignacio-Mejía
Dec 8, 2020·Journal of Child Neurology·Jordana FoxAlison M Dolce
Aug 9, 2020·Medical Hypotheses·Sandra Graf ZupcicVjera Matkovic Ferreri
Feb 7, 2020·Epilepsy & Behavior : E&B·Lin ZhuQian Wu
Jul 4, 2021·Neurologic Clinics·Luis A MartinezAnne E Anderson
Jul 13, 2021·Frontiers in Pharmacology·Jing-Jun ZhengMei Zhang

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
Transfection
Puller
electrophoresis
saturation binding
Assay

Software Mentioned

pClamp
GraphPad Prism
PolyPhen
iStudio
ChromasPro
OriginLab
Oligo
GraphPad
MutationTaster
OriginPro

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.