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
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.
Eur J Hum Genet. 2025 Jan;33(1):131-136. doi: 10.1038/s41431-024-01698-5. Epub 2024 Sep 27.
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).
眼-耳-脊椎综合征（OAVS）的特征是第一和第二鳃弓发育异常。尽管有人反对其为单基因疾病，但少数病例涉及一些基因。我们现在报告8例个体中CHAF1A基因的杂合性、可能的功能丧失变异，其中包括同一家族的3名成员。4例符合OAVS的严格诊断标准，包括不对称耳部发育异常、耳前赘生物、下颌不对称 +/- 椎体畸形。2例患者还出现肾脏畸形。CHAF1A编码CAF-1（染色质组装因子-1）的一个亚基，CAF-1是一种异源三聚体蛋白复合物，负责在复制过程中将新合成的组蛋白H3-H4沉积到新合成的DNA链上。CHAF1A功能丧失变异的鉴定与早期发育基因失调驱动OAVS以及最近归为胚胎畸形复发性组合（RCEM）这一缩写下的其他关联的假设一致。
