Primary cilia defects causing mitral valve prolapse.
Adaptor Proteins, Signal Transducing
/ genetics
Animals
Base Sequence
Cilia
/ pathology
Extracellular Matrix
/ metabolism
Female
Genome-Wide Association Study
Heart Valves
/ diagnostic imaging
Humans
Male
Mice, Knockout
Mitral Valve Prolapse
/ diagnostic imaging
Morphogenesis
Pedigree
Time Factors
Tumor Suppressor Proteins
/ metabolism
Journal
Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086
Informations de publication
Date de publication:
22 05 2019
22 05 2019
Historique:
received:
15
02
2019
accepted:
25
04
2019
entrez:
24
5
2019
pubmed:
24
5
2019
medline:
27
6
2020
Statut:
ppublish
Résumé
Mitral valve prolapse (MVP) affects 1 in 40 people and is the most common indication for mitral valve surgery. MVP can cause arrhythmias, heart failure, and sudden cardiac death, and to date, the causes of this disease are poorly understood. We now demonstrate that defects in primary cilia genes and their regulated pathways can cause MVP in familial and sporadic nonsyndromic MVP cases. Our expression studies and genetic ablation experiments confirmed a role for primary cilia in regulating ECM deposition during cardiac development. Loss of primary cilia during development resulted in progressive myxomatous degeneration and profound mitral valve pathology in the adult setting. Analysis of a large family with inherited, autosomal dominant nonsyndromic MVP identified a deleterious missense mutation in a cilia gene,
Identifiants
pubmed: 31118289
pii: 11/493/eaax0290
doi: 10.1126/scitranslmed.aax0290
pmc: PMC7331025
mid: NIHMS1587658
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
DZIP1 protein, human
0
Dzip1 protein, mouse
0
Tg737Rpw protein, mouse
0
Tumor Suppressor Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL038176
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141917
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL109506
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128099
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL033756
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG002295
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM103342
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL072265
Pays : United States
Organisme : NHLBI NIH HHS
ID : R56 HL122906
Pays : United States
Organisme : NHLBI NIH HHS
ID : K23 HL116652
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007260
Pays : United States
Organisme : BLRD VA
ID : I01 BX000820
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL142159
Pays : United States
Organisme : NHLBI NIH HHS
ID : K24 HL067434
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL127692
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM114429
Pays : United States
Organisme : NIMH NIH HHS
ID : R00 MH095867
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL122906
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK074038
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103444
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM131959
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL131546
Pays : United States
Organisme : NCRR NIH HHS
ID : C06 RR018823
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA045300
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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