دورية
A Monoallelic Two-Hit Mechanism in PLCD1 Explains the Genetic Pathogenesis of Hereditary Trichilemmal Cyst Formation
| العنوان: | A Monoallelic Two-Hit Mechanism in PLCD1 Explains the Genetic Pathogenesis of Hereditary Trichilemmal Cyst Formation |
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| المؤلفون: | Hörer, Steffen, Marrakchi, Slaheddine, Radner, Franz P.W., Zolles, Gerd, Heinz, Lisa, Eichmann, Thomas O., Has, Cristina, Salavei, Pavel, Mahfoudh, Nadia, Turki, Hamida, Zimmer, Andreas D., Fischer, Judith |
| المصدر: | Journal of Investigative Dermatology; October 2019, Vol. 139 Issue: 10 p2154-2163.e5 |
| مستخلص: | Trichilemmal cysts are common hair follicle–derived intradermal cysts. The trait shows an autosomal dominant mode of transmission with incomplete penetrance. Here, we describe the pathogenetic mechanism for the development of hereditary trichilemmal cysts. By whole-exome sequencing of DNA from the blood samples of 5 affected individuals and subsequent Sanger sequencing of a family cohort including 35 affected individuals, this study identified a combination of the Phospholipase C Delta1 germline variants c.903A>G, p.(Pro301Pro) and c.1379C>T, p.(Ser460Leu) as a high-risk factor for trichilemmal cyst development. Allele-specific PCRs and cloning experiments showed that these two variants are present on the same allele. The analysis of tissue from several cysts revealed that an additional somatic Phospholipase C Delta1 mutation on the same allele is required for cyst formation. In two different functional in vitro assays, this study showed that the protein function of the cyst-specific 1-phosphatidylinositol 4, 5-bisphosphate phosphodiesterase delta-1 protein variant is modified. This pathologic mechanism defines a monoallelic model of the two-hit mechanism proposed for tumor development and other hereditary cyst diseases. |
| قاعدة البيانات: | Supplemental Index |
Full Text Finder | تدمد: | 0022202X 15231747 |
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| DOI: | 10.1016/j.jid.2019.04.015 |