SLC12A ion transporter mutations in sporadic and familial human congenital hydrocephalus

Molecular Genetics & Genomic Medicine
Sheng Chih JinKristopher T Kahle

Abstract

Congenital hydrocephalus (CH) is a highly morbid disease that features enlarged brain ventricles and impaired cerebrospinal fluid homeostasis. Although early linkage or targeted sequencing studies in large multigenerational families have localized several genes for CH, the etiology of most CH cases remains unclear. Recent advances in whole exome sequencing (WES) have identified five new bona fide CH genes, implicating impaired regulation of neural stem cell fate in CH pathogenesis. Nonetheless, in the majority of CH cases, the pathological etiology remains unknown, suggesting more genes await discovery. WES of family members of a sporadic and familial form of severe L1CAM mutation-negative CH associated with aqueductal stenosis was performed. Rare genetic variants were analyzed, prioritized, and validated. De novo copy number variants (CNVs) were identified using the XHMM algorithm and validated using qPCR. Xenopus oocyte experiments were performed to access mutation impact on protein function and expression. A novel inherited protein-damaging mutation (p.Pro605Leu) in SLC12A6, encoding the K+ -Cl- cotransporter KCC3, was identified in both affected members of multiplex kindred CHYD110. p.Pro605 is conserved in KCC3 orthologs a...Continue Reading

References

Apr 27, 2007·Journal of Neurochemistry·Stefan LiebauOliver H Wittekindt
Mar 21, 2008·Journal of Neurosurgery. Pediatrics·Tamara D SimonUNKNOWN Hydrocephalus Clinical Research Network
Oct 29, 2009·Proceedings of the National Academy of Sciences of the United States of America·Murim ChoiRichard P Lifton
Jan 19, 2010·Bioinformatics·Heng Li, Richard Durbin
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Aug 17, 2010·Nature Genetics·Sarah B NgJay Shendure
Dec 16, 2010·Journal of the American Academy of Child and Adolescent Psychiatry·Carol A Mathews, Marco A Grados
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
Jul 6, 2012·Brain : a Journal of Neurology·Tina Noergaard MunchMads Melbye
Oct 9, 2012·American Journal of Human Genetics·Menachem FromerShaun M Purcell
Dec 15, 2012·Journal of Medical Genetics·Mohammed S Al-DosariFowzan S Alkuraya
Aug 11, 2015·Lancet·Kristopher T KahleBenjamin C Warf
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
May 31, 2017·Annals of Neurology·Ranad ShaheenFowzan S Alkuraya
Sep 22, 2017·Stem Cells International·Mengchu CuiHua Feng
Dec 1, 2017·Scientific Reports·Morgane AgezAnass Jawhari
Jul 10, 2018·Neuron·Charuta Gavankar FureyKristopher T Kahle

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Citations

Mar 7, 2020·Fluids and Barriers of the CNS·Richard F KeepLester R Drewes
Apr 15, 2020·ELife·Michelle S ReidStephen Graf Brohawn
Jan 31, 2021·International Journal of Molecular Sciences·Sunday Solomon JosiahJinwei Zhang
Mar 1, 2021·Trends in Neurosciences·Mari A VirtanenKai Kaila
Jul 8, 2021·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Adam J KundishoraKristopher T Kahle
Aug 31, 2021·Frontiers in Cell and Developmental Biology·Sneha Ray, Aakanksha Singhvi

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Methods Mentioned

BETA
exome sequencing

Software Mentioned

ANNOVAR
PLINK
PsychENCODE
BWA
GATK HaplotypeCaller
TrioDeNovo
gnomAD
ExAC
MetaSVM
GATK

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