European journal of human genetics : EJHG · 2024
Chromatin assembly factor subunit CHAF1A as a monogenic cause for oculo-auriculo-vertebral spectrum.
СтатьяКлинический случайНазвание и аннотация: Перевод в очереди
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Pingault Véronique, Neiva-Vaz Cécilia, de Oliveira Judite, Martínez-Gil Núria, Lasa-Aranzasti Amaia, Campos Berta, Lakeman Inge M M, Nibbeling Esther A R, Stoeva Radka, Jayakar Parul, Dabir Tabib, Elloumi Houda Zghal, Strong Alanna, Hanein Sylvain, Picard Arnaud, Ochsenbein Francoise, Blanc Pierre, Amiel Jeanne
Аннотация
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).