YIPF5 mutations cause neonatal diabetes and microcephaly: progress for precision medicine and mechanistic understanding.
YIPF5 mutations cause neonatal diabetes and microcephaly: progress for precision medicine and mechanistic understanding.
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YIPF5 突变导致新生儿糖尿病和小头畸形：精准医学和机制理解的进展。
DOI：
10.1172/jci142364
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Taylor,SimeonI
中科院分区：
文献类型：
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作者：
Pollin,ToniI;Taylor,SimeonI
识别导致单基因糖尿病的基因可以提供见解，为精准医学奠定科学基础。目前，近20%的新生儿糖尿病病例病因不明。在本期的JCI杂志中，De Franco和Lytrivi等人对两名患有罕见新生儿糖尿病亚型的先证者的基因组进行了测序，该亚型也与小头畸形和癫痫有关。作者揭示了YIPF5基因的突变。YIPF5位于高尔基体中，被认为在囊泡运输中起关键作用。值得注意的是，在基于β细胞的模型中破坏YIPF5诱导ER应激信号传导并导致细胞内胰岛素原的积累。我们认为，利用登记和生物库来揭示其他单基因非典型形式的糖尿病是一种重要的方法，以获得洞察力，并表明胰岛素增敏剂可能会减轻ER压力与YIPF5中断通过减少胰岛素分泌的需求。
Identifying genes that result in monogenic diabetes can provide insights that can build a scientific foundation for precision medicine. At present, nearly 20% of neonatal diabetes cases have unknown causes. In this issue of theJCI, De Franco and Lytrivi et al. sequenced the genome of two probands with a rare neonatal diabetes subtype that also associated with microcephaly and epilepsy. The authors revealed mutations in theYIPF5gene. YIPF5 resides in the Golgi apparatus and is thought to play a critical role in vesicular trafficking. Notably, disruptingYIPF5in β cell–based models induced ER stress signaling and resulted in the accumulation of intracellular proinsulin. We believe that utilizing registries and biobanks to reveal other monogenic atypical forms of diabetes is an important approach to gaining insight and suggest that an insulin sensitizer may alleviate ER stress associated with YIPF5 disruption by decreasing the demand for insulin secretion.