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Case Reports
. 2025 Jan;33(1):131-136.
doi: 10.1038/s41431-024-01698-5. Epub 2024 Sep 27.

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

Véronique Pingault  1   2   3 , Cécilia Neiva-Vaz  4 , Judite de Oliveira  5 , Núria Martínez-Gil  6   7 , Amaia Lasa-Aranzasti  6   7 , Berta Campos  6   7 , Inge M M Lakeman  8 , Esther A R Nibbeling  8 , Radka Stoeva  9 , Parul Jayakar  10 , Tabib Dabir  11 , Houda Zghal Elloumi  12 , Alanna Strong  13   14 , Sylvain Hanein  15 , Arnaud Picard  4 , Francoise Ochsenbein  16 , Pierre Blanc  17 , Jeanne Amiel  18   5
Affiliations
Case Reports

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

Véronique Pingault et al. Eur J Hum Genet. 2025 Jan.

Abstract

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).

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Conflict of interest statement

Competing interests: There is no competing interest. HZE is an employee of GeneDx, LLC, USA. Ethical approval: These studies have been approved by institutional committees in each country when performed on a research basis. Ethical approvement was not required for case reports based on analysis performed in diagnostic conditions. Consent for publication of photos was obtained.

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