Genetic variants in components of the NALCN-UNC80-UNC79 ion channel complex cause a broad clinical phenotype (NALCN channelopathies)

Human Genetics
Nuria C BramswigDagmar Wieczorek

Abstract

NALCN is a conserved cation channel, which conducts a permanent sodium leak current and regulates resting membrane potential and neuronal excitability. It is part of a large ion channel complex, the "NALCN channelosome", consisting of multiple proteins including UNC80 and UNC79. The predominant neuronal expression pattern and its function suggest an important role in neuronal function and disease. So far, biallelic NALCN and UNC80 variants have been described in a small number of individuals leading to infantile hypotonia, psychomotor retardation, and characteristic facies 1 (IHPRF1, OMIM 615419) and 2 (IHPRF2, OMIM 616801), respectively. Heterozygous de novo NALCN missense variants in the S5/S6 pore-forming segments lead to congenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD, OMIM 616266) with some clinical overlap. In this study, we present detailed clinical information of 16 novel individuals with biallelic NALCN variants, 1 individual with a heterozygous de novo NALCN missense variant and an interesting clinical phenotype without contractures, and 12 individuals with biallelic UNC80 variants. We report for the first time a missense NALCN variant located in the predicted S6 pore-formin...Continue Reading

References

Sep 26, 2008·Nature·Yingxi LinMichael E Greenberg
Oct 28, 2008·American Journal of Human Genetics·Peter N RobinsonStefan Mundlos
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 16, 2012·Science Translational Medicine·Tracy J Dixon-SalazarJoseph G Gleeson
Nov 7, 2012·Nature·UNKNOWN 1000 Genomes Project ConsortiumGil A McVean
Jun 12, 2013·Journal of Medical Genetics·Çiğdem KöroğluAslihan Tolun
Nov 10, 2013·Nature·Brenda L BloodgoodMichael E Greenberg
Mar 29, 2014·Human Mutation·Marten JägerPeter N Robinson
Jun 7, 2014·Frontiers in Cellular Neuroscience·Maud Cochet-BissuelArnaud Monteil
Sep 5, 2014·Science Translational Medicine·Tomasz ZemojtelPeter N Robinson
Nov 29, 2014·Current Protocols in Bioinformatics·Geraldine A Van der AuweraMark A DePristo
Oct 3, 2015·Bioinformatics·Konstantin OkonechnikovFernando García-Alcalde
May 1, 2016·Annals of Neurology·Maha S ZakiJoseph G Gleeson
Aug 12, 2016·American Journal of Medical Genetics. Part a·Elise ValkanasCornelius F Boerkoel
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
Nov 17, 2016·European Journal of Human Genetics : EJHG·Daniel TrujillanoRami Abou Jamra
Sep 9, 2017·American Journal of Medical Genetics. Part a·Angela MyersCornelius F Boerkoel
Nov 24, 2017·American Journal of Medical Genetics. Part a·Toshiki TakenouchiSeiji Mizuno
Feb 6, 2018·Clinical Genetics·A AngiusL Crisponi
Jul 4, 2018·Journal of Human Genetics·Danielle K BourqueHugh J McMillan

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Citations

May 24, 2020·International Journal of Molecular Sciences·Giacomo GaroneFrancesco Nicita
Jul 4, 2020·American Journal of Medical Genetics. Part a·Omotayo OpeAndrew K Sobering
Sep 19, 2020·The Application of Clinical Genetics·Amir Hossein KarimiMajid Foroutan
Jul 23, 2020·Nature·Marc KschonsakJian Payandeh
Dec 5, 2020·Nature Communications·Yunlu KangLei Chen
Nov 19, 2020·Nature Communications·Jiongfang XieZhen Yan
Feb 9, 2019·G3 : Genes - Genomes - Genetics·Laura Faith GeorgeEmily Anne Bates
May 15, 2021·Journal of Biomedical Science·Camilla J WilliamsJeff S Coombes

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Methods Mentioned

BETA
PCR
exome sequencing
electrophoresis
biopsy

Software Mentioned

bcl2fastq
FreeBayes
GATK
Burrows Aligner
PhenIX ( Phenotypic Interpretation of eXomes )
CentoFit
qualimap
BWA
Genome Analysis Software Kit

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