Sökning: onr:"swepub:oai:DiVA.org:liu-190337" > Functional and clin...
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000 | 11388naa a2201477 4500 | |
001 | oai:DiVA.org:liu-190337 | |
003 | SwePub | |
008 | 221205s2023 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-1903372 URI |
024 | 7 | a https://doi.org/10.1038/s41380-022-01852-92 DOI |
040 | a (SwePub)liu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Palmer, Elizabeth E.u Sydney Childrens Hosp Network, Australia; Univ New South Wales, Australia4 aut |
245 | 1 0 | a Functional and clinical studies reveal pathophysiological complexity of CLCN4-related neurodevelopmental condition |
264 | c 2022-11-16 | |
264 | 1 | b SPRINGERNATURE,c 2023 |
338 | a print2 rdacarrier | |
500 | a Funding Agencies|Fondazione AIRC per la Ricerca sul Cancro [IG 21558]; Italian Ministry for University and Research (MIUR) [PRIN 20174TB8KW]; FWO [1861419N]; Queen Elisabeth Medical Foundation; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [418081722, 433158657]; CPA grant [PG01217]; NHMRC Principal Research Fellowship [GNT1120615]; BICARE, Australia; King Salman Center for Disability Research [RG-2022-010, RG-2022-011]; MRC [MR/T007087/1]; GOSH Charity [VS0122]; Rosetrees Trust [CF2\100018]; NHMRC Investigator Grant [GNT20081]; Projekt DEAL; NIHR GOSH BRC | |
520 | a Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a "shift" of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng |
700 | 1 | a Pusch, Michaelu CNR, Italy4 aut |
700 | 1 | a Picollo, Alessandrau CNR, Italy4 aut |
700 | 1 | a Forwood, Caitlinu Sydney Childrens Hosp Network, Australia4 aut |
700 | 1 | a Nguyen, Matthew H.u Univ New South Wales, Australia; Liverpool Hosp, Australia4 aut |
700 | 1 | a Suckow, Vanessau Max Planck Inst Mol Genet, Germany4 aut |
700 | 1 | a Gibbons, Jessicau Max Planck Inst Mol Genet, Germany4 aut |
700 | 1 | a Hoff, Alvau Linköpings universitet,Institutionen för biomedicinska och kliniska vetenskaper,Medicinska fakulteten,CNR, Italy4 aut0 (Swepub:liu)n/a |
700 | 1 | a Sigfrid, Lisau Linköpings universitet,Institutionen för biomedicinska och kliniska vetenskaper,Medicinska fakulteten,CNR, Italy4 aut0 (Swepub:liu)n/a |
700 | 1 | a Megarbane, Andreu Lebanese Amer Univ, Lebanon; Inst Jerome Lejeune, France4 aut |
700 | 1 | a Nizon, Mathildeu Nantes Univ, France; Nantes Univ, France4 aut |
700 | 1 | a Cogne, Benjaminu Nantes Univ, France; Nantes Univ, France4 aut |
700 | 1 | a Beneteau, Claireu Nantes Univ, France4 aut |
700 | 1 | a Alkuraya, Fowzan S.u King Faisal Specialist Hosp & Res Ctr, Saudi Arabia4 aut |
700 | 1 | a Chedrawi, Azizau King Faisal Specialist Hosp & Res Ctr, Saudi Arabia4 aut |
700 | 1 | a Hashem, Mais O.u King Faisal Specialist Hosp & Res Ctr, Saudi Arabia4 aut |
700 | 1 | a Stamberger, Hannahu VIB, Belgium; Antwerp Univ Hosp, Belgium4 aut |
700 | 1 | a Weckhuysen, Sarahu VIB, Belgium; Antwerp Univ Hosp, Belgium; Univ Antwerp, Belgium4 aut |
700 | 1 | a Vanlander, Arnaudu Ghent Univ Hosp, Belgium4 aut |
700 | 1 | a Ceulemans, Bertenu Univ Antwerp, Belgium4 aut |
700 | 1 | a Rajagopalan, Sulekhau Liverpool Hosp, Australia4 aut |
700 | 1 | a Nunn, Kennethu Childrens Hosp Westmead, Australia4 aut |
700 | 1 | a Arpin, Stephanieu Ctr Hosp Reg Univ Tours, France4 aut |
700 | 1 | a Raynaud, Martineu Ctr Hosp Reg Univ Tours, France4 aut |
700 | 1 | a Motter, Constance S.u Akron Childrens Hosp, OH 44308 USA4 aut |
700 | 1 | a Ward-Melver, Catherineu Akron Childrens Hosp, OH 44308 USA4 aut |
700 | 1 | a Janssens, Katrienu Univ Antwerp, Belgium4 aut |
700 | 1 | a Meuwissen, Marijeu Univ Antwerp, Belgium4 aut |
700 | 1 | a Beysen, Dianeu Univ Antwerp, Belgium4 aut |
700 | 1 | a Dikow, Nicolau Heidelberg Univ, Germany4 aut |
700 | 1 | a Grimmel, Monau Univ Tubingen, Germany4 aut |
700 | 1 | a Haack, Tobias B.u Univ Tubingen, Germany4 aut |
700 | 1 | a Clement, Emmau Great Ormond St Hosp Sick Children, England4 aut |
700 | 1 | a McTague, Amyu UCL Great Ormond St Inst Child Hlth, England; Great Ormond St Hosp Sick Children, England4 aut |
700 | 1 | a Hunt, Davidu Princess Anne Hosp, England4 aut |
700 | 1 | a Townshend, Sharronu King Edward Mem Hosp, Australia4 aut |
700 | 1 | a Ward, Michelleu King Edward Mem Hosp, Australia4 aut |
700 | 1 | a Richards, Linda J.u Washington Univ, MI USA; Univ Queensland, Australia4 aut |
700 | 1 | a Simons, Casu Murdoch Childrens Res Inst, Australia; UNSW, Australia4 aut |
700 | 1 | a Costain, Gregoryu Hosp Sick Children, Canada4 aut |
700 | 1 | a Dupuis, Lucieu Hosp Sick Children, Canada4 aut |
700 | 1 | a Mendoza-Londono, Robertou Hosp Sick Children, Canada4 aut |
700 | 1 | a Dudding-Byth, Tracyu Genet Learning Disabil Serv, Australia; Univ Newcastle, Australia4 aut |
700 | 1 | a Boyle, Jackieu Genet Learning Disabil Serv, Australia4 aut |
700 | 1 | a Saunders, Carolu Childrens Mercy Hosp & Clin, MI USA; Univ Missouri, MI USA4 aut |
700 | 1 | a Fleming, Emilyu Childrens Mercy Hosp & Clin, MI USA4 aut |
700 | 1 | a El Chehadeh, Salimau Hop Univ Strasbourg, France; Univ Strasbourg, France; INSERM, France4 aut |
700 | 1 | a Spitz, Marie-Audeu Hop Univ Strasbourg, France4 aut |
700 | 1 | a Piton, Amelieu Hop Univ Strasbourg, France4 aut |
700 | 1 | a Gerard, Benedicteu Hop Univ Strasbourg, France4 aut |
700 | 1 | a Warde, Marie-Therese Abiu Hop Univ Strasbourg, France; CHU Strasbourg, France4 aut |
700 | 1 | a Rea, Gillianu Northern Ireland Reg Genet Serv, North Ireland4 aut |
700 | 1 | a McKenna, Caoimheu Northern Ireland Reg Genet Serv, North Ireland4 aut |
700 | 1 | a Douzgou, Sofiau Haukeland Hosp, Norway; Univ Manchester, England4 aut |
700 | 1 | a Banka, Siddharthu Univ Manchester, England; Manchester Univ NHS Fdn Trust, England4 aut |
700 | 1 | a Akman, Cigdemu Columbia Univ, NY USA4 aut |
700 | 1 | a Bain, Jennifer M.u Columbia Univ, NY USA4 aut |
700 | 1 | a Sands, Tristan T.u Columbia Univ, NY USA4 aut |
700 | 1 | a Wilson, Golder N.u Texas Tech Hlth Sci Ctr Lubbock, TX USA; KinderGenome Med Genet, TX USA4 aut |
700 | 1 | a Silvertooth, Erin J.u Texas Sports Psychiat & Integrat Hlth, TX USA4 aut |
700 | 1 | a Miller, Laurenu Hillcrest Internal Med, TX USA4 aut |
700 | 1 | a Lederer, Damienu Inst Pathol & Genet ASBL, Belgium4 aut |
700 | 1 | a Sachdev, Raniu Sydney Childrens Hosp Network, Australia; Univ New South Wales, Australia4 aut |
700 | 1 | a Macintosh, Rebeccau Sydney Childrens Hosp Network, Australia; Univ New South Wales, Australia4 aut |
700 | 1 | a Monestier, Olivieru Inst Pathol & Genet ASBL, Belgium4 aut |
700 | 1 | a Karadurmus, Denizu Inst Pathol & Genet ASBL, Belgium4 aut |
700 | 1 | a Collins, Felicityu Royal Prince Alfred Hosp, Australia4 aut |
700 | 1 | a Carter, Melissau Childrens Hosp Eastern Ontario, Canada4 aut |
700 | 1 | a Rohena, Luisu San Antonio Mil Med Ctr, TX USA; UT Hlth San Antonio, TX USA4 aut |
700 | 1 | a Willemsen, Marjolein H.u Radboud Univ Nijmegen Med Ctr, Netherlands4 aut |
700 | 1 | a Ockeloen, Charlotte W.u Radboud Univ Nijmegen Med Ctr, Netherlands4 aut |
700 | 1 | a Pfundt, Rolphu Radboud Univ Nijmegen Med Ctr, Netherlands4 aut |
700 | 1 | a Kroft, Sanne D.u Pluryn, Netherlands4 aut |
700 | 1 | a Field, Michaelu Genet Learning Disabil Serv, Australia4 aut |
700 | 1 | a Laranjeira, Francisco E. R.u Ctr Hosp Univ Porto, Portugal4 aut |
700 | 1 | a Fortuna, Ana M.u Univ Porto, Portugal4 aut |
700 | 1 | a Soares, Ana R.u Univ Porto, Portugal4 aut |
700 | 1 | a Michaud, Vincentu CHU Bordeaux, France; Bordeaux Univ, France4 aut |
700 | 1 | a Naudion, Sophieu CHU Bordeaux, France4 aut |
700 | 1 | a Golla, Sailajau CHOC Hosp, CA USA4 aut |
700 | 1 | a Weaver, David D.u Indiana Univ Sch Med, IN 46202 USA4 aut |
700 | 1 | a Bird, Lynne M.u Univ Calif San Diego, CA 92103 USA4 aut |
700 | 1 | a Friedman, Jenniferu Univ Calif San Diego, CA 92103 USA4 aut |
700 | 1 | a Clowes, Virginiau London North West Univ Healthcare NHS Trust, England; Imperial Coll London, England4 aut |
700 | 1 | a Joss, Shelaghu Queen Elizabeth Univ Hosp, Scotland4 aut |
700 | 1 | a Polsler, Laurau Univ Ziekenhuis Brussel, Belgium4 aut |
700 | 1 | a Campeau, Philippe M.u Univ Montreal, Canada4 aut |
700 | 1 | a Blazo, Mariau Texas A&M Univ, TX USA4 aut |
700 | 1 | a Bijlsma, Emilia K.u Leiden Univ Med Ctr, Netherlands4 aut |
700 | 1 | a Rosenfeld, Jill A.u Baylor Coll Med, TX 77030 USA; Baylor Genet Labs, TX USA4 aut |
700 | 1 | a Beetz, Christianu Centogene GmbH, Germany4 aut |
700 | 1 | a Powis, Zoeu Ambry Genet, CA USA4 aut |
700 | 1 | a McWalter, Kirstyu GeneDx LLC, MA USA4 aut |
700 | 1 | a Brandt, Tracyu GeneDx LLC, MA USA4 aut |
700 | 1 | a Torti, Erinu GeneDx LLC, MA USA4 aut |
700 | 1 | a Mathot, Mikaelu CHU UCL Namur, Belgium4 aut |
700 | 1 | a Mohammad, Shekeeb S.u Childrens Hosp Westmead, Australia4 aut |
700 | 1 | a Armstrong, Ruthu Addenbrookes Hosp, England4 aut |
700 | 1 | a Kalscheuer, Vera M.u Max Planck Inst Mol Genet, Germany4 aut |
710 | 2 | a Sydney Childrens Hosp Network, Australia; Univ New South Wales, Australiab CNR, Italy4 org |
773 | 0 | t Molecular Psychiatryd : SPRINGERNATUREg 28:2, s. 668-697q 28:2<668-697x 1359-4184x 1476-5578 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-190337 |
856 | 4 8 | u https://doi.org/10.1038/s41380-022-01852-9 |
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