Chromatin assembly factor subunit CHAF1A as a monogenic cause for oculo-auriculo-vertebral spectrum.


Journal

European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235

Informations de publication

Date de publication:
27 Sep 2024
Historique:
received: 26 04 2024
accepted: 19 09 2024
revised: 20 08 2024
medline: 28 9 2024
pubmed: 28 9 2024
entrez: 27 9 2024
Statut: aheadofprint

Résumé

Oculo-auriculo-vertebral spectrum (OAVS) is characterized by abnormal development of the 1st and 2nd branchial arches. Despite arguments against a monogenic condition, a few genes have been involved in a minority of cases. We now report heterozygous, presumably loss-of function variants in the CHAF1A gene in 8 individuals, including 3 members of the same family. Four cases fulfill stringent diagnostic criteria for OAVS, including asymmetric ear dysplasia, preauricular tags, mandibular asymmetry +/- vertebral malformations. Two patients also presented with kidney malformations. CHAF1A encodes a subunit of CAF-1 (chromatin assembly factor-1), a heterotrimeric protein complex responsible for the deposition of newly synthesized histones H3-H4 onto the newly synthetized DNA strand during replication. The identification of loss-of-unction variants in CHAF1A is consistent with the hypothesis of early developmental genes dysregulation driving OAVS and other associations recently lumped under the acronym Recurrent Constellations of Embryonic Malformations (RCEM).

Identifiants

pubmed: 39333427
doi: 10.1038/s41431-024-01698-5
pii: 10.1038/s41431-024-01698-5
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to European Society of Human Genetics.

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Auteurs

Véronique Pingault (V)

Laboratoire « Embryologie et Génétique des Malformations », Institut Imagine, INSERM UMR1163, Université Paris Cité, Paris, France. veronique.pingault@inserm.fr.
Service de Médecine Génomique des maladies rares, AP-HP.Centre, Hôpital Necker-Enfants Malades, F-75015, Paris, France. veronique.pingault@inserm.fr.
Laboratoire de Biologie Médicale Multi-Sites SeqOIA, Paris, France. veronique.pingault@inserm.fr.

Cécilia Neiva-Vaz (C)

Chirurgie Maxillofaciale, Hôpital Necker-Enfants Malades, AP-HP Centre, Paris, France.

Judite de Oliveira (J)

Service de Médecine Génomique des maladies rares, AP-HP.Centre, Hôpital Necker-Enfants Malades, F-75015, Paris, France.

Núria Martínez-Gil (N)

Department of Clinical and Molecular Genetics, Vall d'Hebron University Hospital, Barcelona, Spain.
Medical Genetics Group, Vall d'Hebron Research Institute, Barcelona, Spain.

Amaia Lasa-Aranzasti (A)

Department of Clinical and Molecular Genetics, Vall d'Hebron University Hospital, Barcelona, Spain.
Medical Genetics Group, Vall d'Hebron Research Institute, Barcelona, Spain.

Berta Campos (B)

Department of Clinical and Molecular Genetics, Vall d'Hebron University Hospital, Barcelona, Spain.
Medical Genetics Group, Vall d'Hebron Research Institute, Barcelona, Spain.

Inge M M Lakeman (IMM)

Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.

Esther A R Nibbeling (EAR)

Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.

Radka Stoeva (R)

Department of Medical Genetics, Le Mans Hospital, Le Mans, France.

Parul Jayakar (P)

Division of Genetics and Metabolism, Nicklaus Children's Hospital, Miami, FL, USA.

Tabib Dabir (T)

Medical Genetics Dept, Belfast City Hospital, Belfast, BT9 7AB, UK.

Houda Zghal Elloumi (HZ)

GeneDx, Gaithersburg, MD, USA.

Alanna Strong (A)

Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Sylvain Hanein (S)

Bioinformatic Platform, Institute of Genetic Diseases, INSERM UMR1163, Institut Imagine, Université Paris-Cité and Structure Fédérative de Recherche Necker, 75015, Paris, France.

Arnaud Picard (A)

Chirurgie Maxillofaciale, Hôpital Necker-Enfants Malades, AP-HP Centre, Paris, France.

Francoise Ochsenbein (F)

Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Institute Joliot, Gif-sur-Yvette, France.

Pierre Blanc (P)

Laboratoire de Biologie Médicale Multi-Sites SeqOIA, Paris, France.

Jeanne Amiel (J)

Laboratoire « Embryologie et Génétique des Malformations », Institut Imagine, INSERM UMR1163, Université Paris Cité, Paris, France.
Service de Médecine Génomique des maladies rares, AP-HP.Centre, Hôpital Necker-Enfants Malades, F-75015, Paris, France.

Classifications MeSH