Chromatin Assembly Factor Subunit CHAF1A As a Monogenic Cause for Oculo-auriculo-vertebral Spectrum

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2024 Sep 27

PMID 39333427

Authors

Veronique Pingault

Cecilia Neiva-Vaz

Judite de Oliveira

Nuria Martinez-Gil

Amaia Lasa-Aranzasti

Berta Campos

Inge M M Lakeman

Esther A R Nibbeling

Radka Stoeva

Parul Jayakar

Tabib Dabir

Houda Zghal Elloumi

Alanna Strong

Sylvain Hanein

Arnaud Picard

Francoise Ochsenbein

Pierre Blanc

Jeanne Amiel

Affiliations

Soon will be listed here.

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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