DOI: 10.1002/ajmg.a.38540 After publishing this manuscript two data errors were identified. Neither error affects the interpretation of the data. Table 3 lists three patients with TCF12 variants. Proband 95628 is listed as a female with a c.1907A>G; p.(Lys636Arg) variant. This proband is male, not female. This proband is correctly listed as a male in Supplemental Table S1a. Table 4 and Supplemental Table S1b list four probands with SCARF2 variants. Proband 95585 is inaccurately listed as having c.2593dupG: p.Ala865Serfs*184. The correct variant designation is c.2596dupG: p.Ala866Glyfs*191

Journal of the European Academy of Dermatology and VenereologyVolume 30, Issue 12 p. e210-e213 Letter to the Editor A novel missense variant in the PNPLA1 gene underlies congenital ichthyosis in three consanguineous families F. Ahmad, F. Ahmad Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, PakistanSearch for more papers by this authorM. Ansar, M. Ansar Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, PakistanSearch for more papers by this authorS. Mehmood, S. Mehmood Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, PakistanSearch for more papers by this authorA. Izoduwa, A. Izoduwa Department of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorK. Lee, K. Lee Department of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorA. Nasir, A. Nasir Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, PakistanSearch for more papers by this authorM. Abrar, M. Abrar Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, PakistanSearch for more papers by this authorS. Mehmood, S. Mehmood Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, PakistanSearch for more papers by this authorA. Ullah, A. Ullah Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, PakistanSearch for more papers by this authorA. Aziz, A. Aziz Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, PakistanSearch for more papers by this authorUniversity of Washington Center for Mendelian Genomics, University of Washington Center for Mendelian Genomics Department of Genome Sciences, University of Washington, Seattle, Washington, USASearch for more papers by this authorJ.D. Smith, J.D. Smith Department of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorJ. Shendure, J. Shendure Department of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorM.J. Bamshad, M.J. Bamshad Department of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorD.A. Nicekrson, D.A. Nicekrson Department of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorR.L.P. Santos-Cortez, R.L.P. Santos-Cortez Department of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorS.M. Leal, S.M. Leal Department of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorW. Ahmad, Corresponding Author W. Ahmad wahmad@qau.edu.pk Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, Pakistan Pakistan Academy of Sciences (PAS), Islamabad, PakistanCorrespondence: W. Ahmad. E-mail: wahmad@qau.edu.pkSearch for more papers by this author F. Ahmad, F. Ahmad Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, PakistanSearch for more papers by this authorM. Ansar, M. Ansar Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, PakistanSearch for more papers by this authorS. Mehmood, S. Mehmood Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, PakistanSearch for more papers by this authorA. Izoduwa, A. Izoduwa Department of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorK. Lee, K. Lee Department of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorA. Nasir, A. Nasir Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, PakistanSearch for more papers by this authorM. Abrar, M. Abrar Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, PakistanSearch for more papers by this authorS. Mehmood, S. Mehmood Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, PakistanSearch for more papers by this authorA. Ullah, A. Ullah Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, PakistanSearch for more papers by this authorA. Aziz, A. Aziz Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, PakistanSearch for more papers by this authorUniversity of Washington Center for Mendelian Genomics, University of Washington Center for Mendelian Genomics Department of Genome Sciences, University of Washington, Seattle, Washington, USASearch for more papers by this authorJ.D. Smith, J.D. Smith Department of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorJ. Shendure, J. Shendure Department of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorM.J. Bamshad, M.J. Bamshad Department of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorD.A. Nicekrson, D.A. Nicekrson Department of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorR.L.P. Santos-Cortez, R.L.P. Santos-Cortez Department of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorS.M. Leal, S.M. Leal Department of Molecular and Human Genetics, Center for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorW. Ahmad, Corresponding Author W. Ahmad wahmad@qau.edu.pk Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, Pakistan Pakistan Academy of Sciences (PAS), Islamabad, PakistanCorrespondence: W. Ahmad. E-mail: wahmad@qau.edu.pkSearch for more papers by this author First published: 21 December 2015 https://doi.org/10.1111/jdv.13540Citations: 10Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume30, Issue12December 2016Pages e210-e213 RelatedInformation

We previously demonstrated that the first intron of the human von Willebrand factor (vWF) is required for gene expression in the endothelium of transgenic mice. Based on this finding, we hypothesized that RNA splicing plays a role in mediating vWF expression in the vasculature. To address this question, we used transient transfection assays in human endothelial cells and megakaryocytes with intron-containing and intronless human vWF promoter-luciferase constructs. Next, we generated knockin mice in which LacZ was targeted to the endogenous mouse vWF locus in the absence or presence of the native first intron or heterologous introns from the human β-globin, mouse Down syndrome critical region 1, or hagfish coagulation factor X genes. In both the in vitro assays and the knockin mice, the loss of the first intron of vWF resulted in a significant reduction of reporter gene expression in endothelial cells but not megakaryocytes. This effect was rescued to varying degrees by the introduction of a heterologous intron. Intron-mediated enhancement of expression was mediated at a posttranscriptional level. Together, these findings implicate a role for intronic splicing in mediating lineage-specific expression of vWF in the endothelium.

BACKGROUND:The central process in chronic renal failure is the progressive accumulation of extracellular matrix in the glomeruli and in the tubulo-interstitial space, resulting in renal fibrosis. Transforming growth factor-beta1 (TGF-beta1) up-regulation plays a major role in the genesis of renal fibrosis. Endoglin is a membrane glycoprotein that binds TGF-beta1 and TGF-beta3 with high affinity. An increased level of endoglin immunostaining has been demonstrated previously in biopsies from patients with chronic progressive renal disease. We have assessed the expression of endoglin in the rat 5/6th renal mass reduction (RMR) model.METHODS:One, 3 and 5 months after RMR, mean arterial pressure and renal function were measured, animals were sacrificed, renal fibrosis was evaluated quantitatively and the expression of endoglin was assessed by western blot, northern blot and immunohistochemistry.RESULTS:RMR induced a progressive increase in mean arterial pressure and urinary protein excretion. Renal corpuscular area, and mesangial and interstitial fibrosis increased with time after RMR. Immunohistochemical staining for endoglin demonstrated its expression mainly on the endothelial surface of major vessels. In kidneys 1 and 3 months after RMR, the expression of endoglin in renal corpuscles was limited to Bowman's parietal epithelium. In rats 5 months after RMR, the immunoexpression in glomerular endothelium was more marked. Northern blot analysis revealed that rats with RMR showed an increase in the expression of mRNA for endoglin, only at 5 months after RMR. Western blot analysis gave a different time course: a marked increase in the first month, a decrease in the 3rd month and a further increase in the 5th month after RMR.CONCLUSIONS:The present study demonstrates increased endoglin expression in rats with severe hypertension and renal damage. This increased endoglin expression coincides with the period of higher renal damage and renal dysfunction.

Endoglin is a transmembrane protein that is found in association with transforming growth factor-beta (TGF-beta) superfamily receptor complexes and has an expression pattern that appears to be restricted primarily to endothelial cells, activated macrophages, trophoblasts, and fibroblasts. Since mutations in endoglin have been shown to be linked to hereditary hemorrhagic telangiectasia type 1, a disease manifested as vascular malformations characterized by excessive layers of vascular smooth muscle cells (VSMC), the expression of endoglin was investigated in VSMC. In vivo, the majority of SMC in human atherosclerotic plaques expressed high levels of endoglin, while endoglin was not detected in SMC from samples of the normal arterial wall. In vitro studies demonstrate that human aortic smooth muscle cells (HASMC) express the L-isoform of endoglin. Like endothelial cells, HASMC express endoglin protein as a dimer on the cell surface that binds TGF-beta1. In vitro, endoglin expression by HASMC is upregulated in response to TGF-beta1, suggesting that the presence of this factor in the atherosclerotic plaque might be responsible for the increased expression of endoglin. The demonstration of increased levels of endoglin in VSMC in human atherosclerotic plaques suggests a role for SMC endoglin in the maintenance of vascular integrity and in the response of the vessel wall to injury.