Extensive identification of genes involved in congenital and structural heart disorders and cardiomyopathy.

Journal

Nature cardiovascular research

ISSN: 2731-0590

Titre abrégé: Nat Cardiovasc Res

Pays: England

ID NLM: 9918284280206676

Informations de publication

Date de publication:
Feb 2022

Historique:

received: 20 04 2021

accepted: 03 01 2022

medline: 1 2 2022

pubmed: 1 2 2022

entrez: 28 8 2024

Statut: ppublish

Résumé

Clinical presentation of congenital heart disease is heterogeneous, making identification of the disease-causing genes and their genetic pathways and mechanisms of action challenging. By using in vivo electrocardiography, transthoracic echocardiography and microcomputed tomography imaging to screen 3,894 single-gene-null mouse lines for structural and functional cardiac abnormalities, here we identify 705 lines with cardiac arrhythmia, myocardial hypertrophy and/or ventricular dilation. Among these 705 genes, 486 have not been previously associated with cardiac dysfunction in humans, and some of them represent variants of unknown relevance (VUR). Mice with mutations in Casz1, Dnajc18, Pde4dip, Rnf38 or Tmem161b genes show developmental cardiac structural abnormalities, with their human orthologs being categorized as VUR. Using UK Biobank data, we validate the importance of the DNAJC18 gene for cardiac homeostasis by showing that its loss of function is associated with altered left ventricular systolic function. Our results identify hundreds of previously unappreciated genes with potential function in congenital heart disease and suggest causal function of five VUR in congenital heart disease.

Identifiants

DOI: 10.1038/s44161-022-00018-8 PMID: 39195995

pubmed: 39195995

doi: 10.1038/s44161-022-00018-8

pii: 10.1038/s44161-022-00018-8

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

157-173

Investigateurs

Juan A Aguilar-Pimentel (JA)

Lore Becker (L)

Lillian Garrett (L)

Sabine M Hölter (SM)

Oana V Amarie (OV)

Julia Calzada-Wack (J)

Tanja Klein-Rodewald (T)

Patricia da Silva-Buttkus (P)

Christoph Lengger (C)

Claudia Stoeger (C)

Raffaele Gerlini (R)

Birgit Rathkolb (B)

Daniela Mayr (D)

John Seavitt (J)

Angelina Gaspero (A)

Jennie R Green (JR)

Arturo Garza (A)

Ritu Bohat (R)

Leeyean Wong (L)

Melissa L McElwee (ML)

Sowmya Kalaga (S)

Tara L Rasmussen (TL)

Isabel Lorenzo (I)

Denise G Lanza (DG)

Rodney C Samaco (RC)

Surabi Veeraragaven (S)

Juan J Gallegos (JJ)

Petr Kašpárek (P)

Silvia Petrezsélyová (S)

Ruairidh King (R)

Sara Johnson (S)

James Cleak (J)

Zsombor Szkoe-Kovacs (Z)

Gemma Codner (G)

Matthew Mackenzie (M)

Adam Caulder (A)

Janet Kenyon (J)

Wendy Gardiner (W)

Hayley Phelps (H)

Rhys Hancock (R)

Claire Norris (C)

Michayla A Moore (MA)

Audrie M Seluke (AM)

Rachel Urban (R)

Coleen Kane (C)

Leslie O Goodwin (LO)

Kevin A Peterson (KA)

Matthew Mckay (M)

Jenn J Cook (JJ)

Jacob P Lowy (JP)

Michael McFarland (M)

Joshua A Wood (JA)

Brandon J Willis (BJ)

Heather Tolentino (H)

Todd Tolentino (T)

Michael Schuchbauer (M)

Jason Salazar (J)

Jennifer Johnson (J)

Rebecca Munson (R)

Abdel Ayadi (A)

Guillaume Pavlovic (G)

Marie-Christine Birling (MC)

Sylvie Jacquot (S)

Dalila Ali-Hadji (D)

Philippe Charles (P)

Philippe Andre (P)

Marie-France Champy (MF)

Fabrice Riet (F)

Igor Vukobradovic (I)

Zorana Berberovic (Z)

Dawei Qu (D)

Ruolin Guo (R)

Abigail D'Souza (A)

Ziyue Huang (Z)

Susan Camilleri (S)

Milan Ganguly (M)

Hibret Adissu (H)

Mohammed Eskandarian (M)

Xueyuan Shang (X)

Kyle Duffin (K)

Catherine Xu (C)

Kyle Roberton (K)

Valerie Laurin (V)

Qing Lan (Q)

Gillian Sleep (G)

Amie Creighton (A)

Lauri Lintott (L)

Marina Gertsenstein (M)

Monica Pereira (M)

Sandra Tondat (S)

Amit Patel (A)

Maribelle Cruz (M)

Alex Bezginov (A)

David Miller (D)

Wang Hy (W)

Atsushi Yoshiki (A)

Nobuhiko Tanaka (N)

Masaru Tamura (M)

Zhiwei Liu (Z)

Olga Ermakova (O)

Anna Ferrara (A)

Paolo Fruscoloni (P)

Claudia Seisenberger (C)

Antje Bürger (A)

Florian Giesert (F)

J C Ambrose (JC)

P Arumu Gam (P)

R Bevers (R)

M Bleda (M)

F Boardman-Pretty (F)

C R Boustred (CR)

H Brittain (H)

M J Caulfield (MJ)

G C Chan (GC)

T Fowler (T)

A Giess (A)

A Hamblin (A)

S Henderson (S)

T J P Hubbard (TJP)

R Jackson (R)

L J Jones (LJ)

D Kasperaviciute (D)

M Kayikci (M)

A Kousathanas (A)

L Lahnstein (L)

S E A Leigh (SEA)

I U S Leong (IUS)

F J Lopez (FJ)

F Maleady-Crowe (F)

M McEntagart (M)

F Minneci (F)

L Moutsianas (L)

M Mueller (M)

N Murugaesu (N)

A C Need (AC)

P O'Donovan (P)

C A Odhams (CA)

C Patch (C)

D Perez-Gil (D)

M B Pereira (MB)

J Pullinger (J)

T Rahim (T)

A Rendon (A)

T Rogers (T)

K Savage (K)

K Sawant (K)

R H Scott (RH)

A Siddiq (A)

A Sieghart (A)

S C Smith (SC)

A Sosinsky (A)

A Stuckey (A)

M Tanguy (M)

A L Taylor-Tavares (AL)

E R A Thomas (ERA)

S R Thompson (SR)

A Tucci (A)

M J Welland (MJ)

E Williams (E)

K Witkowska (K)

S M Wood (SM)

Informations de copyright

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