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Comment
. 2020 Dec 1;130(12):6228-6231.
doi: 10.1172/JCI142364.

YIPF5 mutations cause neonatal diabetes and microcephaly: progress for precision medicine and mechanistic understanding

Toni I Pollin, Simeon I Taylor
Comment

YIPF5 mutations cause neonatal diabetes and microcephaly: progress for precision medicine and mechanistic understanding

Toni I Pollin et al. J Clin Invest. .

Abstract

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 the JCI, 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 the YIPF5 gene. YIPF5 resides in the Golgi apparatus and is thought to play a critical role in vesicular trafficking. Notably, disrupting YIPF5 in 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.

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Conflict of interest statement

Conflict of interest: TIP receives partial research funding from a grant to the University of Maryland, Baltimore, by the Regeneron Genetics Center. SIT serves as a paid consultant to Ionis Pharmaceuticals and is listed as an inventor on a methods of use patent, titled “Use of leptin for treating human lipoatrophy and method of determining predisposition to said treatment” (US 7,183,254 B2).

Comment on

  • YIPF5 mutations cause neonatal diabetes and microcephaly through endoplasmic reticulum stress.
    De Franco E, Lytrivi M, Ibrahim H, Montaser H, Wakeling MN, Fantuzzi F, Patel K, Demarez C, Cai Y, Igoillo-Esteve M, Cosentino C, Lithovius V, Vihinen H, Jokitalo E, Laver TW, Johnson MB, Sawatani T, Shakeri H, Pachera N, Haliloglu B, Ozbek MN, Unal E, Yıldırım R, Godbole T, Yildiz M, Aydin B, Bilheu A, Suzuki I, Flanagan SE, Vanderhaeghen P, Senée V, Julier C, Marchetti P, Eizirik DL, Ellard S, Saarimäki-Vire J, Otonkoski T, Cnop M, Hattersley AT. De Franco E, et al. J Clin Invest. 2020 Dec 1;130(12):6338-6353. doi: 10.1172/JCI141455. J Clin Invest. 2020. PMID: 33164986 Free PMC article.

References

    1. Chung WK, et al. Precision medicine in diabetes: A consensus report from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Diabetes Care. 2020;43(7):1617–1635. doi: 10.2337/dci20-0022. - DOI - PMC - PubMed
    1. Tattersall RB. Mild familial diabetes with dominant inheritance. Q J Med. 1974;43(170):339–357. - PubMed
    1. Tattersall RB, Fajans SS. A difference between the inheritance of classical juvenile-onset and maturity-onset type diabetes of young people. Diabetes. 1975;24(1):44–53. - PubMed
    1. Vionnet N, et al. Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus. Nature. 1992;356(6371):721–722. doi: 10.1038/356721a0. - DOI - PubMed
    1. Yamagata K, et al. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1) Nature. 1996;384(6608):458–460. doi: 10.1038/384458a0. - DOI - PubMed

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