A novel de novo mutation in MYT1, the unique OAVS gene identified so far
A novel de novo mutation in MYT1, the unique OAVS gene identified so far
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DOI：
10.1038/ejhg.2017.101
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发表时间：
2017-09-01
影响因子：
5.2
通讯作者：
Rooryck, Caroline
中科院分区：
文献类型：
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作者：
Berenguer, Marie;Tingaud-Sequeira, Angele;Rooryck, Caroline
眼-耳-椎谱系（OAVS）是一种以半侧颜面矮小伴耳、眼、椎畸形为特征的发育障碍性疾病。最近，MYT 1，编码髓鞘转录因子1，被报道为第一个参与OAVS的基因，在视黄酸（RA）途径。对来自巴西的57名OAVS患者进行MYT 1变异筛查。一个新的从头错义变异影响功能，c。323 C>T（p.（Ser 108 Leu）），在MYT 1中被鉴定，在患有严重形式的OAVS的患者中。功能研究表明，MYT 1过表达下调了参与RA介导的转录的所有RA受体基因（RARA、RARB、RARG），而对参与RA降解的主要酶CYP 26 A1的表达没有影响。总之，影响MYT 1功能的第三种变体被确定为OAVS的原因。此外，我们证实了MYT 1连接到RA信号通路。
Oculo-auriculo-vertebral spectrum (OAVS) is a developmental disorder characterized by hemifacial microsomia associated with ear, eyes and vertebrae malformations showing highly variable expressivity. Recently, MYT1, encoding the myelin transcription factor 1, was reported as the first gene involved in OAVS, within the retinoic acid (RA) pathway. Fifty-seven OAVS patients originating from Brazil were screened for MYT1 variants. A novel de novo missense variant affecting function, c. 323C>T (p. (Ser108Leu)), was identified in MYT1, in a patient presenting with a severe form of OAVS. Functional studies showed that MYT1 overexpression downregulated all RA receptors genes (RARA, RARB, RARG), involved in RA-mediated transcription, whereas no effect was observed on CYP26A1 expression, the major enzyme involved in RA degradation, Moreover, MYT1 variants impacted significantly the expression of these genes, further supporting their pathogenicity. In conclusion, a third variant affecting function in MYT1 was identified as a cause of OAVS. Furthermore, we confirmed MYT1 connection to RA signaling pathway.