Detail
Článek
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Biallelic loss-of-function variants in PLD1 cause congenital right-sided cardiac valve defects and neonatal cardiomyopathy

N. Lahrouchi, AV. Postma, CM. Salazar, DM. De Laughter, F. Tjong, L. Piherová, FZ. Bowling, D. Zimmerman, EM. Lodder, A. Ta-Shma, Z. Perles, L. Beekman, A. Ilgun, Q. Gunst, M. Hababa, D. Škorić-Milosavljević, V. Stránecký, V. Tomek, P. de Knijff,...

. 2021 ; 131 (5) : . [pub] 20210301

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem, Research Support, U.S. Gov't, Non-P.H.S.

Perzistentní odkaz   https://www.medvik.cz/link/bmc21026025

Grantová podpora
UM1 HL098162 NHLBI NIH HHS - United States
T32 GM092714 NIGMS NIH HHS - United States
UM1 HL098123 NHLBI NIH HHS - United States
U01 HL131003 NHLBI NIH HHS - United States
R35 GM128666 NIGMS NIH HHS - United States
UM1 HL128761 NHLBI NIH HHS - United States
UM1 HL128711 NHLBI NIH HHS - United States
UM1 HL098147 NHLBI NIH HHS - United States
R01 GM084251 NIGMS NIH HHS - United States

Congenital heart disease is the most common type of birth defect, accounting for one-third of all congenital anomalies. Using whole-exome sequencing of 2718 patients with congenital heart disease and a search in GeneMatcher, we identified 30 patients from 21 unrelated families of different ancestries with biallelic phospholipase D1 (PLD1) variants who presented predominantly with congenital cardiac valve defects. We also associated recessive PLD1 variants with isolated neonatal cardiomyopathy. Furthermore, we established that p.I668F is a founder variant among Ashkenazi Jews (allele frequency of ~2%) and describe the phenotypic spectrum of PLD1-associated congenital heart defects. PLD1 missense variants were overrepresented in regions of the protein critical for catalytic activity, and, correspondingly, we observed a strong reduction in enzymatic activity for most of the mutant proteins in an enzymatic assay. Finally, we demonstrate that PLD1 inhibition decreased endothelial-mesenchymal transition, an established pivotal early step in valvulogenesis. In conclusion, our study provides a more detailed understanding of disease mechanisms and phenotypic expression associated with PLD1 loss of function.

Amsterdam UMC University of Amsterdam Heart Center Department of Clinical and Experimental Cardiology Amsterdam Cardiovascular Sciences

Children's Heart Centre 2nd Faculty of Medicine Charles University Prague Motol University Hospital Prague Czech Republic

Cyprus School of Molecular Medicine Nicosia Cyprus

Department of Biochemistry and Cell Biology Stony Brook University Stony Brook New York USA

Department of Cell and Developmental Biology Vanderbilt University School of Medicine Nashville Tennessee USA

Department of Clinical Genetics and

Department of Clinical Genetics The Cyprus Institute of Neurology and Genetics Nicosia Cyprus

Department of Genetics Hadassah Hebrew University Medical Center Jerusalem Israel

Department of Human Genetics Leiden University Medical Center Leiden Netherlands

Department of Human Genetics Leiden University Medical Centre Leiden Netherlands

Department of Medical Biology Amsterdam UMC Amsterdam Netherlands

Department of Obstetrics and

Department of Obstetrics Gynecology and Women's Health

Department of Pathology Isala Women and Children's Hospital Zwolle Netherlands

Department of Pediatric Cardiology Emma Children's Hospital Amsterdam UMC University of Amsterdam Amsterdam Netherlands

Department of Pediatric Cardiology Hadassah Hebrew University Medical Center Jerusalem Israel

Department of Pediatric Cardiology Leiden University Medical Centre Leiden Netherlands

Department of Pediatrics Division of Pediatric Cardiology and

Department of Pediatrics Ochsner Clinic Tulane University University of Queensland New Orleans Louisiana USA

Department of Pediatrics University of Minnesota Minneapolis Minnesota USA

Department of Pharmacological Sciences and Graduate Program in Molecular and Cellular Pharmacology Stony Brook University Stony Brook New York USA

Department of Pharmacology Vanderbilt University School of Medicine Nashville Tennessee USA

Division of Cardiology Ann and Robert H Lurie Children's Hospital of Chicago Chicago Illinois USA

Division of Genetics Birth Defects and Metabolic Disorders Ann and Robert H Lurie Children's Hospital of Chicago Chicago Illinois USA

Feinberg School of Medicine Northwestern University Chicago Illinois USA

Genetic and Rare Disease Research Division Bambino Gesù Children's Hospital IRCCS Rome Italy

Makarios Medical Centre Nicosia Cyprus

Medical Genetics Department UPMC Children's Hospital of Pittsburgh Pittsburgh Pennsylvania USA

Research Unit for Rare Diseases Department of Pediatrics and Adolescent Medicine 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Service de Génétique Médicale CHU Estaing Clermont Ferrand France

Ultrasound and Fetal Medicine Diagnostic Centre Nicosia Cyprus

UMR 1231 INSERM GAD Université Bourgogne Franche Comté Dijon France

Unité Fonctionnelle d'Innovation en Diagnostique Génomique des Maladies Rares FHU TRANSLAD Centre Hospitalier Universitaire Estaing Dijon Bourgogne Dijon France

University Medical Center Groningen Department of Genetics University of Groningen Groningen Netherlands

000      
00000naa a2200000 a 4500
001      
bmc21026025
003      
CZ-PrNML
005      
20211026133250.0
007      
ta
008      
211013s2021 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1172/JCI142148 $2 doi
035    __
$a (PubMed)33645542
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Lahrouchi, Najim $u Amsterdam UMC, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences
245    10
$a Biallelic loss-of-function variants in PLD1 cause congenital right-sided cardiac valve defects and neonatal cardiomyopathy / $c N. Lahrouchi, AV. Postma, CM. Salazar, DM. De Laughter, F. Tjong, L. Piherová, FZ. Bowling, D. Zimmerman, EM. Lodder, A. Ta-Shma, Z. Perles, L. Beekman, A. Ilgun, Q. Gunst, M. Hababa, D. Škorić-Milosavljević, V. Stránecký, V. Tomek, P. de Knijff, R. de Leeuw, JY. Robinson, SC. Burn, H. Mustafa, M. Ambrose, T. Moss, J. Jacober, DM. Niyazov, B. Wolf, KH. Kim, S. Cherny, A. Rousounides, A. Aristidou-Kallika, G. Tanteles, B. Ange-Line, AS. Denommé-Pichon, C. Francannet, D. Ortiz, MC. Haak, AD. Ten Harkel, GT. Manten, AC. Dutman, K. Bouman, M. Magliozzi, FC. Radio, GW. Santen, JC. Herkert, HA. Brown, O. Elpeleg, MJ. van den Hoff, B. Mulder, MV. Airola, S. Kmoch, JV. Barnett, SA. Clur, MA. Frohman, CR. Bezzina
520    9_
$a Congenital heart disease is the most common type of birth defect, accounting for one-third of all congenital anomalies. Using whole-exome sequencing of 2718 patients with congenital heart disease and a search in GeneMatcher, we identified 30 patients from 21 unrelated families of different ancestries with biallelic phospholipase D1 (PLD1) variants who presented predominantly with congenital cardiac valve defects. We also associated recessive PLD1 variants with isolated neonatal cardiomyopathy. Furthermore, we established that p.I668F is a founder variant among Ashkenazi Jews (allele frequency of ~2%) and describe the phenotypic spectrum of PLD1-associated congenital heart defects. PLD1 missense variants were overrepresented in regions of the protein critical for catalytic activity, and, correspondingly, we observed a strong reduction in enzymatic activity for most of the mutant proteins in an enzymatic assay. Finally, we demonstrate that PLD1 inhibition decreased endothelial-mesenchymal transition, an established pivotal early step in valvulogenesis. In conclusion, our study provides a more detailed understanding of disease mechanisms and phenotypic expression associated with PLD1 loss of function.
650    12
$a alely $7 D000483
650    _2
$a ženské pohlaví $7 D005260
650    12
$a vrozené srdeční vady $x enzymologie $x genetika $7 D006330
650    12
$a nemoci srdečních chlopní $x enzymologie $x genetika $7 D006349
650    _2
$a lidé $7 D006801
650    12
$a mutace ztráty funkce $7 D000073658
650    _2
$a mužské pohlaví $7 D008297
650    12
$a fosfolipasa D $x genetika $x metabolismus $7 D010739
655    _2
$a časopisecké články $7 D016428
655    _2
$a Research Support, N.I.H., Extramural $7 D052061
655    _2
$a práce podpořená grantem $7 D013485
655    _2
$a Research Support, U.S. Gov't, Non-P.H.S. $7 D013486
700    1_
$a Postma, Alex V $u Department of Clinical Genetics, and $u Department of Medical Biology, Amsterdam UMC, Amsterdam, Netherlands
700    1_
$a Salazar, Christian M $u Department of Pharmacological Sciences and Graduate Program in Molecular and Cellular Pharmacology, Stony Brook University, Stony Brook, New York, USA
700    1_
$a De Laughter, Daniel M $u Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
700    1_
$a Tjong, Fleur $u Amsterdam UMC, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences
700    1_
$a Piherová, Lenka $u Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
700    1_
$a Bowling, Forrest Z $u Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, USA
700    1_
$a Zimmerman, Dominic $u Amsterdam UMC, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences
700    1_
$a Lodder, Elisabeth M $u Amsterdam UMC, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences
700    1_
$a Ta-Shma, Asaf $u Department of Pediatric Cardiology, Hadassah, Hebrew University Medical Center, Jerusalem, Israel
700    1_
$a Perles, Zeev $u Department of Pediatric Cardiology, Hadassah, Hebrew University Medical Center, Jerusalem, Israel
700    1_
$a Beekman, Leander $u Amsterdam UMC, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences
700    1_
$a Ilgun, Aho $u Department of Medical Biology, Amsterdam UMC, Amsterdam, Netherlands
700    1_
$a Gunst, Quinn $u Department of Medical Biology, Amsterdam UMC, Amsterdam, Netherlands
700    1_
$a Hababa, Mariam $u Amsterdam UMC, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences
700    1_
$a Škorić-Milosavljević, Doris $u Amsterdam UMC, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences
700    1_
$a Stránecký, Viktor $u Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
700    1_
$a Tomek, Viktor $u Children's Heart Centre, 2nd Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czech Republic
700    1_
$a de Knijff, Peter $u Department of Human Genetics, Leiden University Medical Centre, Leiden, Netherlands
700    1_
$a de Leeuw, Rick $u Department of Human Genetics, Leiden University Medical Centre, Leiden, Netherlands
700    1_
$a Robinson, Jamille Y $u Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
700    1_
$a Burn, Sabrina C $u Department of Obstetrics, Gynecology and Women's Health
700    1_
$a Mustafa, Hiba $u Department of Obstetrics, Gynecology and Women's Health
700    1_
$a Ambrose, Matthew $u Department of Pediatrics, Division of Pediatric Cardiology, and
700    1_
$a Moss, Timothy $u Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA
700    1_
$a Jacober, Jennifer $u Department of Pediatrics, Ochsner Clinic, Tulane University, University of Queensland, New Orleans, Louisiana, USA
700    1_
$a Niyazov, Dmitriy M $u Department of Pediatrics, Ochsner Clinic, Tulane University, University of Queensland, New Orleans, Louisiana, USA
700    1_
$a Wolf, Barry $u Division of Genetics, Birth Defects and Metabolic Disorders, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA $u Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
700    1_
$a Kim, Katherine H $u Division of Genetics, Birth Defects and Metabolic Disorders, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA $u Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
700    1_
$a Cherny, Sara $u Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA $u Division of Cardiology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA
700    1_
$a Rousounides, Andreas $u Makarios Medical Centre, Nicosia, Cyprus
700    1_
$a Aristidou-Kallika, Aphrodite $u Ultrasound and Fetal Medicine Diagnostic Centre, Nicosia, Cyprus
700    1_
$a Tanteles, George $u Cyprus School of Molecular Medicine, Nicosia, Cyprus $u Department of Clinical Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
700    1_
$a Ange-Line, Bruel $u UMR 1231 INSERM, GAD, Université Bourgogne Franche-Comté, Dijon, France $u Unité Fonctionnelle d'Innovation en Diagnostique Génomique des Maladies Rares, FHU-TRANSLAD, Centre Hospitalier Universitaire Estaing (CHU), Dijon Bourgogne, Dijon, France
700    1_
$a Denommé-Pichon, Anne-Sophie $u UMR 1231 INSERM, GAD, Université Bourgogne Franche-Comté, Dijon, France $u Unité Fonctionnelle d'Innovation en Diagnostique Génomique des Maladies Rares, FHU-TRANSLAD, Centre Hospitalier Universitaire Estaing (CHU), Dijon Bourgogne, Dijon, France
700    1_
$a Francannet, Christine $u Service de Génétique Médicale, CHU Estaing, Clermont-Ferrand, France
700    1_
$a Ortiz, Damara $u Medical Genetics Department, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
700    1_
$a Haak, Monique C $u Department of Obstetrics and
700    1_
$a Ten Harkel, Arend D.J. $u Department of Pediatric Cardiology, Leiden University Medical Centre, Leiden, Netherlands
700    1_
$a Manten, Gwendolyn Tr $u Department of Obstetrics and
700    1_
$a Dutman, Annemiek C $u Department of Pathology, Isala Women and Children's Hospital, Zwolle, Netherlands
700    1_
$a Bouman, Katelijne $u University Medical Center Groningen, Department of Genetics, University of Groningen, Groningen, Netherlands
700    1_
$a Magliozzi, Monia $u Genetic and Rare Disease Research Division, Bambino Gesù Children's Hospital IRCCS, Rome, Italy
700    1_
$a Radio, Francesca Clementina $u Genetic and Rare Disease Research Division, Bambino Gesù Children's Hospital IRCCS, Rome, Italy
700    1_
$a Santen, Gijs We $u Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands
700    1_
$a Herkert, Johanna C $u University Medical Center Groningen, Department of Genetics, University of Groningen, Groningen, Netherlands
700    1_
$a Brown, H Alex $u Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
700    1_
$a Elpeleg, Orly $u Department of Genetics, Hadassah, Hebrew University Medical Center, Jerusalem, Israel
700    1_
$a van den Hoff, Maurice Jb $u Department of Medical Biology, Amsterdam UMC, Amsterdam, Netherlands
700    1_
$a Mulder, Barbara $u Amsterdam UMC, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences
700    1_
$a Airola, Michael V $u Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, USA
700    1_
$a Kmoch, Stanislav $u Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
700    1_
$a Barnett, Joey V $u Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
700    1_
$a Clur, Sally-Ann $u Department of Pediatric Cardiology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
700    1_
$a Frohman, Michael A $u Department of Pharmacological Sciences and Graduate Program in Molecular and Cellular Pharmacology, Stony Brook University, Stony Brook, New York, USA
700    1_
$a Bezzina, Connie R $u Amsterdam UMC, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences
773    0_
$w MED00002590 $t The Journal of clinical investigation $x 1558-8238 $g Roč. 131, č. 5 (2021)
856    41
$u https://pubmed.ncbi.nlm.nih.gov/33645542 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20211013 $b ABA008
991    __
$a 20211026133256 $b ABA008
999    __
$a ok $b bmc $g 1714901 $s 1146532
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2021 $b 131 $c 5 $e 20210301 $i 1558-8238 $m The Journal of clinical investigation $n J Clin Invest $x MED00002590
GRA    __
$a UM1 HL098162 $p NHLBI NIH HHS $2 United States
GRA    __
$a T32 GM092714 $p NIGMS NIH HHS $2 United States
GRA    __
$a UM1 HL098123 $p NHLBI NIH HHS $2 United States
GRA    __
$a U01 HL131003 $p NHLBI NIH HHS $2 United States
GRA    __
$a R35 GM128666 $p NIGMS NIH HHS $2 United States
GRA    __
$a UM1 HL128761 $p NHLBI NIH HHS $2 United States
GRA    __
$a UM1 HL128711 $p NHLBI NIH HHS $2 United States
GRA    __
$a UM1 HL098147 $p NHLBI NIH HHS $2 United States
GRA    __
$a R01 GM084251 $p NIGMS NIH HHS $2 United States
LZP    __
$a Pubmed-20211013

Najít záznam

Citační ukazatele

Možnosti archivace