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1,556 results on '"Lifton, Richard P."'

401. Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity

Author

Braun, Daniela A., Schueler, Markus, Halbritter, Jan, Gee, Heon Yung, Porath, Jonathan D., Lawson, Jennifer A., Airik, Rannar, Shril, Shirlee, Allen, Susan J., Stein, Deborah, Al Kindy, Adila, Beck, Bodo B., Cengiz, Nurcan, Moorani, Khemchand N., Ozaltin, Fatih, Hashmi, Seema, Sayer, John A., Bockenhauer, Detlef, Soliman, Neveen A., Otto, Edgar A., Lifton, Richard P., Hildebrandt, Friedhelm, Braun, Daniela A., Schueler, Markus, Halbritter, Jan, Gee, Heon Yung, Porath, Jonathan D., Lawson, Jennifer A., Airik, Rannar, Shril, Shirlee, Allen, Susan J., Stein, Deborah, Al Kindy, Adila, Beck, Bodo B., Cengiz, Nurcan, Moorani, Khemchand N., Ozaltin, Fatih, Hashmi, Seema, Sayer, John A., Bockenhauer, Detlef, Soliman, Neveen A., Otto, Edgar A., Lifton, Richard P., and Hildebrandt, Friedhelm

Abstract

Chronically increased echogenicity on renal ultrasound is a sensitive early finding of chronic kidney disease that can be detected before manifestation of other symptoms. Increased echogenicity, however, is not specific for a certain etiology of chronic kidney disease. Here, we, performed whole exome sequencing in 79 consanguineous or familial cases of suspected nephronophthisis in order to determine the underlying molecular disease cause. In 50 cases, there was a causative mutation in a known monogenic disease gene. In 32 of these cases whole exome sequencing confirmed the diagnosis of a nephronophthisis-related ciliopathy. In 8 cases it revealed the diagnosis of a renal tubulopathy. The remaining 10 cases were identified as Alport syndrome (4), autosomal-recessive polycystic kidney disease (2), congenital anomalies of the kidney and urinary tract (3), and APECED syndrome (1). In 5 families, in whom mutations in known monogenic genes were excluded, we applied homozygosity mapping for variant filtering and identified 5 novel candidate genes (RBM48, FAM186B, PIASI, INCENP, and RCORI) for renal ciliopathies. Thus, whole exome sequencing allows the detection of the causative mutation in 2/3 of affected individuals, thereby presenting the etiologic diagnosis, and allows identification of novel candidate genes.

Published
2016

402. Exome sequencing identifies potential novel candidate genes in patients with unexplained colorectal adenomatous polyposis

Author

Spier, Isabel, Kerick, Martin, Drichel, Dmitriy, Horpaopan, Sukanya, Altmueller, Janine, Laner, Andreas, Holzapfel, Stefanie, Peters, Sophia, Adam, Ronja, Zhao, Bixiao, Becker, Tim, Lifton, Richard P., Holinski-Feder, Elke, Perner, Sven, Thiele, Holger, Noethen, Markus M., Hoffmann, Per, Timmermann, Bernd, Schweiger, Michal R., Aretz, Stefan, Spier, Isabel, Kerick, Martin, Drichel, Dmitriy, Horpaopan, Sukanya, Altmueller, Janine, Laner, Andreas, Holzapfel, Stefanie, Peters, Sophia, Adam, Ronja, Zhao, Bixiao, Becker, Tim, Lifton, Richard P., Holinski-Feder, Elke, Perner, Sven, Thiele, Holger, Noethen, Markus M., Hoffmann, Per, Timmermann, Bernd, Schweiger, Michal R., and Aretz, Stefan

Abstract

In up to 30 % of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, and POLE or POLD1, causing Polymerase-Proofreading-associated polyposis can be identified, although a hereditary etiology is likely. To uncover new causative genes, exome sequencing was performed using DNA from leukocytes and a total of 12 colorectal adenomas from seven unrelated patients with unexplained sporadic adenomatous polyposis. For data analysis and variant filtering, an established bioinformatics pipeline including in-house tools was applied. Variants were filtered for rare truncating point mutations and copy-number variants assuming a dominant, recessive, or tumor suppressor model of inheritance. Subsequently, targeted sequence analysis of the most promising candidate genes was performed in a validation cohort of 191 unrelated patients. All relevant variants were validated by Sanger sequencing. The analysis of exome sequencing data resulted in the identification of rare loss-of-function germline mutations in three promising candidate genes (DSC2, PIEZO1, ZSWIM7). In the validation cohort, further variants predicted to be pathogenic were identified in DSC2 and PIEZO1. According to the somatic mutation spectra, the adenomas in this patient cohort follow the classical pathways of colorectal tumorigenesis. The present study identified three candidate genes which might represent rare causes for a predisposition to colorectal adenoma formation. Especially PIEZO1 (FAM38A) and ZSWIM7 (SWS1) warrant further exploration. To evaluate the clinical relevance of these genes, investigation of larger patient cohorts and functional studies are required.

Published
2016

403. Exome Sequencing Identifies Biallelic MSH3 Germline Mutations as a Recessive Subtype of Colorectal Adenomatous Polyposis

Author

Adam, Ronja, Spier, Isabel, Zhao, Bixiao, Kloth, Michael, Marquez, Jonathan, Hinrichsen, Inga, Kirfel, Jutta, Tafazzoli, Aylar, Horpaopan, Sukanya, Uhlhaas, Siegfried, Stienen, Dietlinde, Friedrichs, Nicolaus, Altmueller, Janine, Laner, Andreas, Holzapfel, Stefanie, Peters, Sophia, Kayser, Katrin, Thiele, Holger, Holinski-Feder, Elke, Marra, Giancarlo, Kristiansen, Glen, Noethen, Markus M., Buettner, Reinhard, Moeslein, Gabriela, Betz, Regina C., Brieger, Angela, Lifton, Richard P., Aretz, Stefan, Adam, Ronja, Spier, Isabel, Zhao, Bixiao, Kloth, Michael, Marquez, Jonathan, Hinrichsen, Inga, Kirfel, Jutta, Tafazzoli, Aylar, Horpaopan, Sukanya, Uhlhaas, Siegfried, Stienen, Dietlinde, Friedrichs, Nicolaus, Altmueller, Janine, Laner, Andreas, Holzapfel, Stefanie, Peters, Sophia, Kayser, Katrin, Thiele, Holger, Holinski-Feder, Elke, Marra, Giancarlo, Kristiansen, Glen, Noethen, Markus M., Buettner, Reinhard, Moeslein, Gabriela, Betz, Regina C., Brieger, Angela, Lifton, Richard P., and Aretz, Stefan

Abstract

In similar to 30% of families affected by colorectal adenomatous polyposis, no germline mutations have been identified in the previously implicated genes APC, MUTYH, POLE, POLD1, and NTHL1, although a hereditary etiology is likely. To uncover further genes with high-penetrance causative mutations, we performed exome sequencing of leukocyte DNA from 102 unrelated individuals with unexplained adenomatous polyposis. We identified two unrelated individuals with differing compound- heterozygous loss-of-function (LoF) germline mutations in the mismatch-repair gene MSH3. The impact of the MSH3 mutations (c.1148delA, c.2319 -1G> A, c.2760delC, and c.3001-2A>C) was indicated at the RNA and protein levels. Analysis of the diseased individuals' tumor tissue demonstrated high microsatellite instability of di-and tetranucleotides (EMAST), and immunohistochemical staining illustrated a complete loss of nuclear MSH3 in normal and tumor tissue, confirming the LoF effect and causal relevance of the mutations. The pedigrees, genotypes, and frequency of MSH3 mutations in the general population are consistent with an autosomal-recessive mode of inheritance. Both index persons have an affected sibling carrying the same mutations. The tumor spectrum in these four persons comprised colorectal and duodenal adenomas, colorectal cancer, gastric cancer, and an early-onset astrocytoma. Additionally, we detected one unrelated individual with biallelic PMS2 germline mutations, representing constitutional mismatch-repair deficiency. Potentially causative variants in 14 more candidate genes identified in 26 other individuals require further workup. In the present study, we identified biallelic germline MSH3 mutations in individuals with a suspected hereditary tumor syndrome. Our data suggest that MSH3 mutations represent an additional recessive subtype of colorectal adenomatous polyposis.

Published
2016

404. Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma.

Author

Bi, Mark, Bi, Mark, Zhao, Siming, Said, Jonathan W, Merino, Maria J, Adeniran, Adebowale J, Xie, Zuoquan, Nawaf, Cayce B, Choi, Jaehyuk, Belldegrun, Arie S, Pantuck, Allan J, Kluger, Harriet M, Bilgüvar, Kaya, Lifton, Richard P, Shuch, Brian, Bi, Mark, Bi, Mark, Zhao, Siming, Said, Jonathan W, Merino, Maria J, Adeniran, Adebowale J, Xie, Zuoquan, Nawaf, Cayce B, Choi, Jaehyuk, Belldegrun, Arie S, Pantuck, Allan J, Kluger, Harriet M, Bilgüvar, Kaya, Lifton, Richard P, and Shuch, Brian

Abstract

The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10(-4)), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10(-17)); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers.

Published
2016

405. Potassium depletion stimulates Na-Cl cotransporter via phosphorylation and inactivation of the ubiquitin ligase Kelch-like 3

Author

Ishizawa, Kenichi, Xu, Ning, Loffing, Johannes, Lifton, Richard P, Fujita, Toshiro, Uchida, Shunya, Shibata, Shigeru, Ishizawa, Kenichi, Xu, Ning, Loffing, Johannes, Lifton, Richard P, Fujita, Toshiro, Uchida, Shunya, and Shibata, Shigeru

Abstract

Kelch-like 3 (KLHL3) is a component of an E3 ubiquitin ligase complex that regulates blood pressure by targeting With-No-Lysine (WNK) kinases for degradation. Mutations in KLHL3 cause constitutively increased renal salt reabsorption and impaired K+ secretion, resulting in hypertension and hyperkalemia. Although clinical studies have shown that dietary K+ intake affects blood pressure, the mechanisms have been obscure. In this study, we demonstrate that the KLHL3 ubiquitin ligase complex is involved in the low-K+-mediated activation of Na-Cl cotransporter (NCC) in the kidney. In the distal convoluted tubules of mice eating a low-K$^+$ diet, we found increased KLHL3 phosphorylation at S433 (KLHL3$^{S433-P}$), a modification that impairs WNK binding, and also reduced total KLHL3 levels. These changes are accompanied by the accumulation of the target substrate WNK4, and activation of the downstream kinases SPAK (STE20/SPS1-related proline-alanine-rich protein kinase) and OSR1 (oxidative stress-responsive 1), resulting in NCC phosphorylation and its accumulation at the plasma membrane. Increased phosphorylation of S433 was explained by increased levels of active, phosphorylated protein kinase C (but not protein kinase A), which directly phosphorylates S433. Moreover, in HEK cells expressing KLHL3 and WNK4, we showed that the activation of protein kinase C by phorbol 12-myristate 13-acetate induces KLHL3$^{S433-P}$ and increases WNK4 levels by abrogating its ubiquitination. These data demonstrate the role of KLHL3 in low-K$^+$-mediated induction of NCC; this physiologic adaptation reduces distal electrogenic Na+ reabsorption, preventing further renal K+ loss but promoting increased blood pressure.

Published
2016

406. FAT1 mutations cause a glomerulotubular nephropathy

Author

Gee, Heon Yung, Sadowski, Carolin E, Aggarwal, Pardeep K, Porath, Jonathan D, Yakulov, Toma A, Schueler, Markus, Lovric, Svjetlana, Ashraf, Shazia, Braun, Daniela A, Halbritter, Jan, Fang, Humphrey, Airik, Rannar, Vega-Warner, Virginia, Jee Cho, Kyeong, Chan, Timothy A, Morris, Luc G T, Ffrench-Constant, Charles, Allen, Nicholas, McNeill, Helen, Büscher, Rainer, Kyrieleis, Henriette, Wallot, Michael, Gaspert, Ariana, Kistler, Thomas, Milford, David V, Saleem, Moin A, Keng, Wee Teik, Alexander, Stephen I, Valentini, Rudolph P, Licht, Christoph, Teh, Jun C, Bogdanovic, Radovan, Koziell, Ania, Bierzynska, Agnieszka, Soliman, Neveen A, Otto, Edgar A, Lifton, Richard P, Holzman, Lawrence B, Sibinga, Nicholas E S, Walz, Gerd, Tufro, Alda, Hildebrandt, Friedhelm, Gee, Heon Yung, Sadowski, Carolin E, Aggarwal, Pardeep K, Porath, Jonathan D, Yakulov, Toma A, Schueler, Markus, Lovric, Svjetlana, Ashraf, Shazia, Braun, Daniela A, Halbritter, Jan, Fang, Humphrey, Airik, Rannar, Vega-Warner, Virginia, Jee Cho, Kyeong, Chan, Timothy A, Morris, Luc G T, Ffrench-Constant, Charles, Allen, Nicholas, McNeill, Helen, Büscher, Rainer, Kyrieleis, Henriette, Wallot, Michael, Gaspert, Ariana, Kistler, Thomas, Milford, David V, Saleem, Moin A, Keng, Wee Teik, Alexander, Stephen I, Valentini, Rudolph P, Licht, Christoph, Teh, Jun C, Bogdanovic, Radovan, Koziell, Ania, Bierzynska, Agnieszka, Soliman, Neveen A, Otto, Edgar A, Lifton, Richard P, Holzman, Lawrence B, Sibinga, Nicholas E S, Walz, Gerd, Tufro, Alda, and Hildebrandt, Friedhelm

Abstract

Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease (CKD). Here we show that recessive mutations in FAT1 cause a distinct renal disease entity in four families with a combination of SRNS, tubular ectasia, haematuria and facultative neurological involvement. Loss of FAT1 results in decreased cell adhesion and migration in fibroblasts and podocytes and the decreased migration is partially reversed by a RAC1/CDC42 activator. Podocyte-specific deletion of Fat1 in mice induces abnormal glomerular filtration barrier development, leading to podocyte foot process effacement. Knockdown of Fat1 in renal tubular cells reduces migration, decreases active RAC1 and CDC42, and induces defects in lumen formation. Knockdown of fat1 in zebrafish causes pronephric cysts, which is partially rescued by RAC1/CDC42 activators, confirming a role of the two small GTPases in the pathogenesis. These findings provide new insights into the pathogenesis of SRNS and tubulopathy, linking FAT1 and RAC1/CDC42 to podocyte and tubular cell function.

Published
2016

408. Paracellin-1, a Renal Tight Junction Protein Required for Paracellular [Mg.sup.2+] Resorption

Author

Simon, David B., Lu, Yin, Choate, Keith A., Velazquez, Heino, Al-Sabban, Essam, Praga, Manuel, Casari, Giorgio, Bettinelli, Alberto, Colussi, Giacomo, Rodriguez-Soriano, Juan, McCredie, David, Milford, David, Sanjad, Sami, and Lifton, Richard P.

Subjects
Epithelium -- Analysis, Cell migration -- Analysis, Science and technology, Analysis
Abstract

Epithelia permit selective and regulated flux from apical to basolateral surfaces by transcellular passage through cells or paracellular flux between cells. Tight junctions constitute the barrier to paracellular conductance; however, little is known about the specific molecules that mediate paracellular permeabilities. Renal magnesium ion ([Mg.sup.2+]) resorption occurs predominantly through a paracellular conductance in the thick ascending limb of Henle (TAL). Here, positional cloning has identified a human gene, paracellin-1 (PCLN-1), mutations in which cause renal [Mg.sup.2+] wasting. PCLN-1 is located in tight junctions of the TAL and is related to the claudin family of tight junction proteins. These findings provide insight into [Mg.sup.2+] homeostasis, demonstrate the role of a tight junction protein in human disease, and identify an essential component of a selective paracellular conductance., The composition of fluids on opposite sides of epithelial cell layers is often different, and is maintained by barriers to passage of fluid, electrolytes, nutrients, pathogens, and cells. Cellular membranes [...]

Published
1999

409. Genetic landscape of metastatic and recurrent head and neck squamous cell carcinoma

Author

Hedberg, Matthew L., Goh, Gerald, Chiosea, Simion I., Bauman, Julie E., Freilino, Maria L., Zeng, Yan, Wang, Lin, Diergaarde, Brenda B., Gooding, William E., Lui, Vivian W.Y., Herbst, Roy S., Lifton, Richard P., and Grandis, Jennifer R.

Subjects
Health care industry
Abstract

Original citation: J Clin Invest. 2016;126(1):169-180. doi:10.1172/JCI82066. An incorrect accession number for the sequencing data appeared twice in the manuscript, once in Results and once in Methods. The two corrected [...]

Published
2016

413. Mutational landscape of uterine and ovarian carcinosarcomas implicates histone genes in epithelial–mesenchymal transition

Author

Zhao, Siming, primary, Bellone, Stefania, additional, Lopez, Salvatore, additional, Thakral, Durga, additional, Schwab, Carlton, additional, English, Diana P., additional, Black, Jonathan, additional, Cocco, Emiliano, additional, Choi, Jungmin, additional, Zammataro, Luca, additional, Predolini, Federica, additional, Bonazzoli, Elena, additional, Bi, Mark, additional, Buza, Natalia, additional, Hui, Pei, additional, Wong, Serena, additional, Abu-Khalaf, Maysa, additional, Ravaggi, Antonella, additional, Bignotti, Eliana, additional, Bandiera, Elisabetta, additional, Romani, Chiara, additional, Todeschini, Paola, additional, Tassi, Renata, additional, Zanotti, Laura, additional, Odicino, Franco, additional, Pecorelli, Sergio, additional, Donzelli, Carla, additional, Ardighieri, Laura, additional, Facchetti, Fabio, additional, Falchetti, Marcella, additional, Silasi, Dan-Arin, additional, Ratner, Elena, additional, Azodi, Masoud, additional, Schwartz, Peter E., additional, Mane, Shrikant, additional, Angioli, Roberto, additional, Terranova, Corrado, additional, Quick, Charles Matthew, additional, Edraki, Babak, additional, Bilgüvar, Kaya, additional, Lee, Moses, additional, Choi, Murim, additional, Stiegler, Amy L., additional, Boggon, Titus J., additional, Schlessinger, Joseph, additional, Lifton, Richard P., additional, and Santin, Alessandro D., additional

Published
2016
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414. Mutations in the Histone Modifier PRDM6 Are Associated with Isolated Nonsyndromic Patent Ductus Arteriosus

Author

Li, Na, primary, Subrahmanyan, Lakshman, additional, Smith, Emily, additional, Yu, Xiaoqing, additional, Zaidi, Samir, additional, Choi, Murim, additional, Mane, Shrikant, additional, Nelson-Williams, Carol, additional, Behjati, Mohaddeseh, additional, Kazemi, Mohammad, additional, Hashemi, Mohammad, additional, Fathzadeh, Mohsen, additional, Narayanan, Anand, additional, Tian, Likun, additional, Montazeri, Farhad, additional, Mani, Mitra, additional, Begleiter, Michael L., additional, Coon, Brian G., additional, Lynch, Henry T., additional, Olson, Eric N., additional, Zhao, Hongyu, additional, Ruland, Jürgen, additional, Lifton, Richard P., additional, and Mani, Arya, additional

Published
2016
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415. Loss of RNA expression and allele-specific expression associated with congenital heart disease

Author

McKean, David M., primary, Homsy, Jason, additional, Wakimoto, Hiroko, additional, Patel, Neil, additional, Gorham, Joshua, additional, DePalma, Steven R., additional, Ware, James S., additional, Zaidi, Samir, additional, Ma, Wenji, additional, Patel, Nihir, additional, Lifton, Richard P., additional, Chung, Wendy K., additional, Kim, Richard, additional, Shen, Yufeng, additional, Brueckner, Martina, additional, Goldmuntz, Elizabeth, additional, Sharp, Andrew J., additional, Seidman, Christine E., additional, Gelb, Bruce D., additional, and Seidman, J. G., additional

Published
2016
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416. ACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment

Author

Vilarinho, Sílvia, primary, Sari, Sinan, additional, Mazzacuva, Francesca, additional, Bilgüvar, Kaya, additional, Esendagli-Yilmaz, Güldal, additional, Jain, Dhanpat, additional, Akyol, Gülen, additional, Dalgiç, Buket, additional, Günel, Murat, additional, Clayton, Peter T., additional, and Lifton, Richard P., additional

Published
2016
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417. Two locus inheritance of non-syndromic midline craniosynostosis via rare SMAD6 and common BMP2 alleles

Author

Timberlake, Andrew T, primary, Choi, Jungmin, additional, Zaidi, Samir, additional, Lu, Qiongshi, additional, Nelson-Williams, Carol, additional, Brooks, Eric D, additional, Bilguvar, Kaya, additional, Tikhonova, Irina, additional, Mane, Shrikant, additional, Yang, Jenny F, additional, Sawh-Martinez, Rajendra, additional, Persing, Sarah, additional, Zellner, Elizabeth G, additional, Loring, Erin, additional, Chuang, Carolyn, additional, Galm, Amy, additional, Hashim, Peter W, additional, Steinbacher, Derek M, additional, DiLuna, Michael L, additional, Duncan, Charles C, additional, Pelphrey, Kevin A, additional, Zhao, Hongyu, additional, Persing, John A, additional, and Lifton, Richard P, additional

Published
2016
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418. ETV4 Mutation in a Patient with Congenital Anomalies of the Kidney and Urinary Tract

Author

Chen, Jing, primary, Van der Ven, Amelie T., additional, Newman, Joseph A., additional, Vivante, Asaf, additional, Mann, Nina, additional, Aitkenhead, Hazel, additional, Shril, Shirlee, additional, Ityel, Hadas, additional, Schulz, Julian, additional, Schmidt, Johanna Magdalena, additional, Widmeier, Eugen, additional, Gileadi, Opher, additional, Costantini, Frank, additional, Thowfeequ, Shifaan, additional, Wenger, Roland H., additional, Bauer, Stuart B., additional, Lee, Richard S., additional, Lu, Weining, additional, Getwan, Maike, additional, Kaminski, Michael M., additional, Lienkamp, Soeren S., additional, Lifton, Richard P., additional, Tasic, Velibor, additional, Kehinde, Elijah O., additional, and Hildebrandt, Friedhelm, additional

Published
2016
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420. Author response: Two locus inheritance of non-syndromic midline craniosynostosis via rare SMAD6 and common BMP2 alleles

Author

Timberlake, Andrew T, primary, Choi, Jungmin, additional, Zaidi, Samir, additional, Lu, Qiongshi, additional, Nelson-Williams, Carol, additional, Brooks, Eric D, additional, Bilguvar, Kaya, additional, Tikhonova, Irina, additional, Mane, Shrikant, additional, Yang, Jenny F, additional, Sawh-Martinez, Rajendra, additional, Persing, Sarah, additional, Zellner, Elizabeth G, additional, Loring, Erin, additional, Chuang, Carolyn, additional, Galm, Amy, additional, Hashim, Peter W, additional, Steinbacher, Derek M, additional, DiLuna, Michael L, additional, Duncan, Charles C, additional, Pelphrey, Kevin A, additional, Zhao, Hongyu, additional, Persing, John A, additional, and Lifton, Richard P, additional

Published
2016
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421. Shifting patterns of genomic variation in the somatic evolution of papillary thyroid carcinoma

Author

Rubinstein, Jill C., primary, Brown, Taylor C., additional, Christison-Lagay, Emily R., additional, Zhang, Yawei, additional, Kunstman, John W., additional, Juhlin, C. Christofer, additional, Nelson-Williams, Carol, additional, Goh, Gerald, additional, Quinn, Courtney E., additional, Callender, Glenda G., additional, Udelsman, Robert, additional, Lifton, Richard P., additional, Korah, Reju, additional, and Carling, Tobias, additional

Published
2016
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422. Exome Sequencing Identifies Biallelic MSH3 Germline Mutations as a Recessive Subtype of Colorectal Adenomatous Polyposis

Author

Adam, Ronja, primary, Spier, Isabel, additional, Zhao, Bixiao, additional, Kloth, Michael, additional, Marquez, Jonathan, additional, Hinrichsen, Inga, additional, Kirfel, Jutta, additional, Tafazzoli, Aylar, additional, Horpaopan, Sukanya, additional, Uhlhaas, Siegfried, additional, Stienen, Dietlinde, additional, Friedrichs, Nicolaus, additional, Altmüller, Janine, additional, Laner, Andreas, additional, Holzapfel, Stefanie, additional, Peters, Sophia, additional, Kayser, Katrin, additional, Thiele, Holger, additional, Holinski-Feder, Elke, additional, Marra, Giancarlo, additional, Kristiansen, Glen, additional, Nöthen, Markus M., additional, Büttner, Reinhard, additional, Möslein, Gabriela, additional, Betz, Regina C., additional, Brieger, Angela, additional, Lifton, Richard P., additional, and Aretz, Stefan, additional

Published
2016
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423. Mutational landscape of uterine and ovarian carcinosarcomas.

Author

Menderes, Gulden, primary, Zhao, Siming, additional, Schwab, Carlton, additional, Lopez, Salvatore, additional, Black, Jonathan, additional, Bellone, Stefania, additional, Silasi, Dan-Arin, additional, Ratner, Elena, additional, Azodi, Masoud, additional, Litkouhi, Babak, additional, Schwartz, Peter E., additional, Schlessinger, Joseph, additional, Lifton, Richard P, additional, and Santin, Alessandro, additional

Published
2016
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424. De Novo and Rare Variants at Multiple Loci Support the Oligogenic Origins of Atrioventricular Septal Heart Defects

Author

Priest, James R., primary, Osoegawa, Kazutoyo, additional, Mohammed, Nebil, additional, Nanda, Vivek, additional, Kundu, Ramendra, additional, Schultz, Kathleen, additional, Lammer, Edward J., additional, Girirajan, Santhosh, additional, Scheetz, Todd, additional, Waggott, Daryl, additional, Haddad, Francois, additional, Reddy, Sushma, additional, Bernstein, Daniel, additional, Burns, Trudy, additional, Steimle, Jeffrey D., additional, Yang, Xinan H., additional, Moskowitz, Ivan P., additional, Hurles, Matthew, additional, Lifton, Richard P., additional, Nickerson, Debbie, additional, Bamshad, Michael, additional, Eichler, Evan E., additional, Mital, Seema, additional, Sheffield, Val, additional, Quertermous, Thomas, additional, Gelb, Bruce D., additional, Portman, Michael, additional, and Ashley, Euan A., additional

Published
2016
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425. FAT1 mutations cause a glomerulotubular nephropathy

Author

Gee, Heon Yung, primary, Sadowski, Carolin E., additional, Aggarwal, Pardeep K., additional, Porath, Jonathan D., additional, Yakulov, Toma A., additional, Schueler, Markus, additional, Lovric, Svjetlana, additional, Ashraf, Shazia, additional, Braun, Daniela A., additional, Halbritter, Jan, additional, Fang, Humphrey, additional, Airik, Rannar, additional, Vega-Warner, Virginia, additional, Cho, Kyeong Jee, additional, Chan, Timothy A., additional, Morris, Luc G. T., additional, ffrench-Constant, Charles, additional, Allen, Nicholas, additional, McNeill, Helen, additional, Büscher, Rainer, additional, Kyrieleis, Henriette, additional, Wallot, Michael, additional, Gaspert, Ariana, additional, Kistler, Thomas, additional, Milford, David V., additional, Saleem, Moin A., additional, Keng, Wee Teik, additional, Alexander, Stephen I., additional, Valentini, Rudolph P., additional, Licht, Christoph, additional, Teh, Jun C., additional, Bogdanovic, Radovan, additional, Koziell, Ania, additional, Bierzynska, Agnieszka, additional, Soliman, Neveen A., additional, Otto, Edgar A., additional, Lifton, Richard P., additional, Holzman, Lawrence B., additional, Sibinga, Nicholas E. S., additional, Walz, Gerd, additional, Tufro, Alda, additional, and Hildebrandt, Friedhelm, additional

Published
2016
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426. Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome

Author

Braun, Daniela A, primary, Sadowski, Carolin E, additional, Kohl, Stefan, additional, Lovric, Svjetlana, additional, Astrinidis, Susanne A, additional, Pabst, Werner L, additional, Gee, Heon Yung, additional, Ashraf, Shazia, additional, Lawson, Jennifer A, additional, Shril, Shirlee, additional, Airik, Merlin, additional, Tan, Weizhen, additional, Schapiro, David, additional, Rao, Jia, additional, Choi, Won-Il, additional, Hermle, Tobias, additional, Kemper, Markus J, additional, Pohl, Martin, additional, Ozaltin, Fatih, additional, Konrad, Martin, additional, Bogdanovic, Radovan, additional, Büscher, Rainer, additional, Helmchen, Udo, additional, Serdaroglu, Erkin, additional, Lifton, Richard P, additional, Antonin, Wolfram, additional, and Hildebrandt, Friedhelm, additional

Published
2016
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427. Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma

Author

Bi, Mark, primary, Zhao, Siming, additional, Said, Jonathan W., additional, Merino, Maria J., additional, Adeniran, Adebowale J., additional, Xie, Zuoquan, additional, Nawaf, Cayce B., additional, Choi, Jaehyuk, additional, Belldegrun, Arie S., additional, Pantuck, Allan J., additional, Kluger, Harriet M., additional, Bilgüvar, Kaya, additional, Lifton, Richard P., additional, and Shuch, Brian, additional

Published
2016
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429. Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity

Author

Braun, Daniela A., primary, Schueler, Markus, additional, Halbritter, Jan, additional, Gee, Heon Yung, additional, Porath, Jonathan D., additional, Lawson, Jennifer A., additional, Airik, Rannar, additional, Shril, Shirlee, additional, Allen, Susan J., additional, Stein, Deborah, additional, Al Kindy, Adila, additional, Beck, Bodo B., additional, Cengiz, Nurcan, additional, Moorani, Khemchand N., additional, Ozaltin, Fatih, additional, Hashmi, Seema, additional, Sayer, John A., additional, Bockenhauer, Detlef, additional, Soliman, Neveen A., additional, Otto, Edgar A., additional, Lifton, Richard P., additional, and Hildebrandt, Friedhelm, additional

Published
2016
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430. Exome sequencing identifies potential novel candidate genes in patients with unexplained colorectal adenomatous polyposis

Author

Spier, Isabel, primary, Kerick, Martin, additional, Drichel, Dmitriy, additional, Horpaopan, Sukanya, additional, Altmüller, Janine, additional, Laner, Andreas, additional, Holzapfel, Stefanie, additional, Peters, Sophia, additional, Adam, Ronja, additional, Zhao, Bixiao, additional, Becker, Tim, additional, Lifton, Richard P., additional, Holinski-Feder, Elke, additional, Perner, Sven, additional, Thiele, Holger, additional, Nöthen, Markus M., additional, Hoffmann, Per, additional, Timmermann, Bernd, additional, Schweiger, Michal R., additional, and Aretz, Stefan, additional

Published
2016
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431. Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma.

Author

Bi, Xiao, primary, Zhao, Siming, additional, Adeniran, Adebowale, additional, Kluger, Harriet M., additional, Xie, Zuoquan, additional, Nawaf, Cayce, additional, Merino, Maria J, additional, Valera, Vladimir, additional, Pantuck, Allan J., additional, Said, Jonathan W., additional, Belldegrun, Arie S., additional, Lifton, Richard P, additional, and Shuch, Brian M., additional

Published
2016
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432. Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in insulin-producing adenomas

Author

Cromer, M. Kyle, Choi, Murim, Nelson-Williams, Carol, Fonseca, Annabelle L., Kunstman, John W., Korah, Reju M., Overton, John D., Mane, Shrikant, Kenney, Barton, Malchoff, Carl D., Stålberg, Peter, Åkerström, Göran, Westin, Gunnar, Hellman, Per, Carling, Tobias, Björklund, Peyman, Lifton, Richard P., Cromer, M. Kyle, Choi, Murim, Nelson-Williams, Carol, Fonseca, Annabelle L., Kunstman, John W., Korah, Reju M., Overton, John D., Mane, Shrikant, Kenney, Barton, Malchoff, Carl D., Stålberg, Peter, Åkerström, Göran, Westin, Gunnar, Hellman, Per, Carling, Tobias, Björklund, Peyman, and Lifton, Richard P.

Abstract

Insulinomas are pancreatic islet tumors that inappropriately secrete insulin, producing hypoglycemia. Exome and targeted sequencing revealed that 14 of 43 insulinomas harbored the identical somatic mutation in the DNA-binding zinc finger of the transcription factor Yin Yang 1 (YY1). Chromatin immunoprecipitation sequencing (ChIP-Seq) showed that this T372R substitution changes the DNA motif bound by YY1. Global analysis of gene expression demonstrated distinct clustering of tumors with and without YY1(T372R) mutations. Genes showing large increases in expression in YY1(T372R) tumors included ADCY1 (an adenylyl cyclase) and CACNA2D2 (a Ca2+ channel); both are expressed at very low levels in normal beta-cells and show mutation-specific YY1 binding sites. Both gene products are involved in key pathways regulating insulin secretion. Expression of these genes in rat INS-1 cells demonstrated markedly increased insulin secretion. These findings indicate that YY1(T372R) mutations are neomorphic, resulting in constitutive activation of cAMP and Ca2+ signaling pathways involved in insulin secretion.

Published
2015
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433. Whole-exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene

Author

Christofer Juhlin, C., Stenman, Adam, Haglund, Felix, Clark, Victoria E., Brown, Taylor C., Baranoski, Jacob, Bilguvar, Kaya, Goh, Gerald, Welander, Jenny, Svahn, Fredrika, Rubinstein, Jill C., Caramuta, Stefano, Yasuno, Katsuhito, Guenel, Murat, Backdahl, Martin, Gimm, Oliver, Söderkvist, Peter, Prasad, Manju L., Korah, Reju, Lifton, Richard P., Carling, Tobias, Christofer Juhlin, C., Stenman, Adam, Haglund, Felix, Clark, Victoria E., Brown, Taylor C., Baranoski, Jacob, Bilguvar, Kaya, Goh, Gerald, Welander, Jenny, Svahn, Fredrika, Rubinstein, Jill C., Caramuta, Stefano, Yasuno, Katsuhito, Guenel, Murat, Backdahl, Martin, Gimm, Oliver, Söderkvist, Peter, Prasad, Manju L., Korah, Reju, Lifton, Richard P., and Carling, Tobias

Abstract

As subsets of pheochromocytomas (PCCs) lack a defined molecular etiology, we sought to characterize the mutational landscape of PCCs to identify novel gene candidates involved in disease development. A discovery cohort of 15 PCCs wild type for mutations in PCC susceptibility genes underwent whole-exome sequencing, and an additional 83 PCCs served as a verification cohort for targeted sequencing of candidate mutations. A low rate of nonsilent single nucleotide variants (SNVs) was detected (6.1/sample). Somatic HRAS and EPAS1 mutations were observed in one case each, whereas the remaining 13 cases did not exhibit variants in established PCC genes. SNVs aggregated in apoptosis-related pathways, and mutations in COSMIC genes not previously reported in PCCs included ZAN, MITF, WDTC1, and CAMTA1. Two somatic mutations and one constitutional variant in the well-established cancer gene lysine (K)-specific methyltransferase 2D (KMT2D, MLL2) were discovered in one sample each, prompting KMT2D screening using focused exome-sequencing in the verification cohort. An additional 11 PCCs displayed KMT2D variants, of which two were recurrent. In total, missense KMT2D variants were found in 14 (11 somatic, two constitutional, one undetermined) of 99 PCCs (14%). Five cases displayed somatic mutations in the functional FYR/SET domains of KMT2D, constituting 36% of all KMT2D-mutated PCCs. KMT2D expression was upregulated in PCCs compared to normal adrenals, and KMT2D overexpression positively affected cell migration in a PCC cell line. We conclude that KMT2D represents a recurrently mutated gene with potential implication for PCC development. (c) 2015 The Authors. Genes, Chromosomes and Cancer Published by Wiley Periodicals, Inc., Funding Agencies|Stockholm County Council; StratCan, Karolinska Institutet, Stockholm; Agency for Science, Technology and Research, Singapore; Cancer Society in Stockholm, Sweden; Damon Runyon Cancer Research Foundation; Ohse Research Award

Published
2015
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434. DCDC2 mutations cause a renal-hepatic ciliopathy by disrupting Wnt signaling

Author

Schueler, Markus, Braun, Daniela A, Chandrasekar, Gayathri, Gee, Heon Yung, Klasson, Timothy D., Halbritter, Jan, Bieder, Andrea, Porath, Jonathan D, Airik, Rannar, Zhou, Weibin, LoTurco, Joseph J, Che, Alicia, Otto, Edgar A, Böckenhauer, Detlef, Sebire, Neil J, Honzik, Tomas, Harris, Peter C, Koon, Sarah J, Gunay-Aygun, Meral, Saunier, Sophie, Zerres, Klaus, Bruechle, Nadina Ortiz, Drenth, Joost P H, Pelletier, Laurence, Tapia-Páez, Isabel, Lifton, Richard P, Giles, R, Kere, Juha, Hildebrandt, Friedhelm, Schueler, Markus, Braun, Daniela A, Chandrasekar, Gayathri, Gee, Heon Yung, Klasson, Timothy D., Halbritter, Jan, Bieder, Andrea, Porath, Jonathan D, Airik, Rannar, Zhou, Weibin, LoTurco, Joseph J, Che, Alicia, Otto, Edgar A, Böckenhauer, Detlef, Sebire, Neil J, Honzik, Tomas, Harris, Peter C, Koon, Sarah J, Gunay-Aygun, Meral, Saunier, Sophie, Zerres, Klaus, Bruechle, Nadina Ortiz, Drenth, Joost P H, Pelletier, Laurence, Tapia-Páez, Isabel, Lifton, Richard P, Giles, R, Kere, Juha, and Hildebrandt, Friedhelm

Published
2015

435. Mutations of the SLIT2–ROBO2 pathway genes SLIT2 and SRGAP1 confer risk for congenital anomalies of the kidney and urinary tract

Author

Hwang, Daw Yang, Kohl, Stefan, Fan, Xueping, Vivante, Asaf, Chan, Stefanie, Dworschak, Gabriel C., Schulz, Julian, van Eerde, Albertien M., Hilger, Alina C., Gee, Heon Yung, Pennimpede, Tracie, Herrmann, Bernhard G., van de Hoek, Glenn, Renkema, Kirsten Y., Schell, Christoph, Huber, Tobias B., Reutter, Heiko M., Soliman, Neveen A., Stajic, Natasa, Bogdanovic, Radovan, Kehinde, Elijah O., Lifton, Richard P., Tasic, Velibor, Lu, Weining, Hildebrandt, Friedhelm, Hwang, Daw Yang, Kohl, Stefan, Fan, Xueping, Vivante, Asaf, Chan, Stefanie, Dworschak, Gabriel C., Schulz, Julian, van Eerde, Albertien M., Hilger, Alina C., Gee, Heon Yung, Pennimpede, Tracie, Herrmann, Bernhard G., van de Hoek, Glenn, Renkema, Kirsten Y., Schell, Christoph, Huber, Tobias B., Reutter, Heiko M., Soliman, Neveen A., Stajic, Natasa, Bogdanovic, Radovan, Kehinde, Elijah O., Lifton, Richard P., Tasic, Velibor, Lu, Weining, and Hildebrandt, Friedhelm

Published
2015

436. New genetic loci link adipose and insulin biology to body fat distribution

Author

UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Shungin, Dmitry, Winkler, Thomas W., Croteau-Chonka, Damien C., Ferreira, Teresa, Locke, Adam E., Mägi, Reedik, Strawbridge, Rona J., Pers, Tune H., Fischer, Krista, Justice, Anne E., Workalemahu, Tsegaselassie, Wu, Joseph M. W., Buchkovich, Martin L., Heard-Costa, Nancy L., Roman, Tamara S., Drong, Alexander W., Song, Ci, Gustafsson, Stefan, Day, Felix R., Esko, Tonu, Fall, Tove, Kutalik, Zoltán, Luan, Jian’an, Randall, Joshua C., Scherag, André, Vedantam, Sailaja, Wood, Andrew R., Chen, Jin, Fehrmann, Rudolf, Karjalainen, Juha, Kahali, Bratati, Liu, Ching-Ti, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bragg-Gresham, Jennifer L., Buyske, Steven, Demirkan, Ayse, Ehret, Georg B., Feitosa, Mary F., Goel, Anuj, Jackson, Anne U., Johnson, Toby, Kleber, Marcus E., Kristiansson, Kati, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Palmer, Cameron D., Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J., Prokopenko, Inga, Stančáková, Alena, Ju Sung, Yun, Tanaka, Toshiko, Teumer, Alexander, Van Vliet-Ostaptchouk, Jana V., Yengo, Loïc, Zhang, Weihua, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M., Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blüher, Matthias, Böhringer, Stefan, Bonnet, Fabrice, Böttcher, Yvonne, Bruinenberg, Marcel, Carba, Delia B., Caspersen, Ida H., Clarke, Robert, Warwick Daw, E., Deelen, Joris, Deelman, Ewa, Delgado, Graciela, Doney, Alex S. F., Eklund, Niina, Erdos, Michael R., Estrada, Karol, Eury, Elodie, Friedrich, Nele, Garcia, Melissa E., Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S., Golay, Alain, Grallert, Harald, Grammer, Tanja B., Gräßler, Jürgen, Grewal, Jagvir, Groves, Christopher J., Haller, Toomas, Hallmans, Goran, Hartman, Catharina A., Hassinen, Maija, Hayward, Caroline, Heikkilä, Kauko, Herzig, Karl-Heinz, Helmer, Quinta, Hillege, Hans L., Holmen, Oddgeir, Hunt, Steven C., Isaacs, Aaron, Ittermann, Till, James, Alan L., Johansson, Ingegerd, Juliusdottir, Thorhildur, Kalafati, Ioanna-Panagiota, Kinnunen, Leena, Koenig, Wolfgang, Kooner, Ishminder K., Kratzer, Wolfgang, Lamina, Claudia, Leander, Karin, Lee, Nanette R., Lichtner, Peter, Lind, Lars, Lindström, Jaana, Lobbens, Stéphane, Lorentzon, Mattias, Mach, François, Magnusson, Patrik K. E., Mahajan, Anubha, McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Mills, Rebecca, Moayyeri, Alireza, Monda, Keri L., Mooijaart, Simon P., Mühleisen, Thomas W., Mulas, Antonella, Müller, Gabriele, Müller-Nurasyid, Martina, Nagaraja, Ramaiah, Nalls, Michael A., Narisu, Narisu, Glorioso, Nicola, Nolte, Ilja M., Olden, Matthias, Rayner, Nigel W., Renstrom, Frida, Ried, Janina S., Robertson, Neil R., Rose, Lynda M., Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Sennblad, Bengt, Seufferlein, Thomas, Sitlani, Colleen M., Vernon Smith, Albert, Stirrups, Kathleen, Stringham, Heather M., Sundström, Johan, Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tayo, Bamidele O., Thorand, Barbara, Thorleifsson, Gudmar, Tomaschitz, Andreas, Troffa, Chiara, van Oort, Floor V. A., Verweij, Niek, Vonk, Judith M., Waite, Lindsay L., Wennauer, Roman, Wilsgaard, Tom, Wojczynski, Mary K., Wong, Andrew, Zhang, Qunyuan, Hua Zhao, Jing, Brennan, Eoin P., Choi, Murim, Eriksson, Per, Folkersen, Lasse, Franco-Cereceda, Anders, Gharavi, Ali G., Hedman, Åsa K., Hivert, Marie-France, Huang, Jinyan, Kanoni, Stavroula, Karpe, Fredrik, Keildson, Sarah, Kiryluk, Krzysztof, Liang, Liming, Lifton, Richard P., Ma, Baoshan, McKnight, Amy J., McPherson, Ruth, Metspalu, Andres, Min, Josine L., Moffatt, Miriam F., Montgomery, Grant W., Murabito, Joanne M., Nicholson, George, Nyholt, Dale R., Olsson, Christian, Perry, John R. B., Reinmaa, Eva, Salem, Rany M., Sandholm, Niina, Schadt, Eric E., Scott, Robert A., Stolk, Lisette, Vallejo, Edgar E., Westra, Harm-Jan, Zondervan, Krina T., Amouyel, Philippe, Arveiler, Dominique, Bakker, Stephan J. L., Beilby, John, Bergman, Richard N., Blangero, John, Brown, Morris J., Burnier, Michel, Campbell, Harry, Chakravarti, Aravinda, Chines, Peter S., Claudi-Boehm, Simone, Collins, Francis S., Crawford, Dana C., Danesh, John, de Faire, Ulf, de Geus, Eco J. C., Dörr, Marcus, Erbel, Raimund, Eriksson, Johan G., Farrall, Martin, Ferrannini, Ele, Ferrières, Jean, Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Gansevoort, Ron T., Gieger, Christian, Gudnason, Vilmundur, Haiman, Christopher A., Harris, Tamara B., Hattersley, Andrew T., Heliövaara, Markku, Hicks, Andrew A., Hingorani, Aroon D., Hoffmann, Wolfgang, Hofman, Albert, Homuth, Georg, Humphries, Steve E., Hyppönen, Elina, Illig, Thomas, Jarvelin, Marjo-Riitta, Johansen, Berit, Jousilahti, Pekka, Jula, Antti M., Kaprio, Jaakko, Kee, Frank, Keinanen-Kiukaanniemi, Sirkka M., Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kraja, Aldi T., Kumari, Meena, Kuulasmaa, Kari, Kuusisto, Johanna, Lakka, Timo A., Langenberg, Claudia, Le Marchand, Loic, Lehtimäki, Terho, Lyssenko, Valeriya, Männistö, Satu, Marette, André, Matise, Tara C., McKenzie, Colin A., McKnight, Barbara, Musk, Arthur W., Möhlenkamp, Stefan, Morris, Andrew D., Nelis, Mari, Ohlsson, Claes, Oldehinkel, Albertine J., Ong, Ken K., Palmer, Lyle J., Penninx, Brenda W., Peters, Annette, Pramstaller, Peter P., Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Ridker, Paul M., Ritchie, Marylyn D., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Saramies, Jouko, Sarzynski, Mark A., Schwarz, Peter E. H., Shuldiner, Alan R., Staessen, Jan A., Steinthorsdottir, Valgerdur, Stolk, Ronald P., Strauch, Konstantin, Tönjes, Anke, Tremblay, Angelo, Tremoli, Elena, Vohl, Marie-Claude, Völker, Uwe, Vollenweider, Peter, Wilson, James F., Witteman, Jacqueline C., Adair, Linda S., Bochud, Murielle, Boehm, Bernhard O., Bornstein, Stefan R., Bouchard, Claude, Cauchi, Stéphane, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Cooper, Richard S., Dedoussis, George, Ferrucci, Luigi, Froguel, Philippe, Grabe, Hans-Jörgen, Hamsten, Anders, Hui, Jennie, Hveem, Kristian, Jöckel, Karl-Heinz, Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, März, Winfried, Munroe, Patricia B., Njølstad, Inger, Oostra, Ben A., Palmer, Colin N. A., Pedersen, Nancy L., Perola, Markus, Pérusse, Louis, Peters, Ulrike, Power, Chris, Quertermous, Thomas, Rauramaa, Rainer, Rivadeneira, Fernando, Saaristo, Timo E., Saleheen, Danish, Sinisalo, Juha, Eline Slagboom, P., Snieder, Harold, Spector, Tim D., Thorsteinsdottir, Unnur, Stumvoll, Michael, Tuomilehto, Jaakko, Uitterlinden, André G., Uusitupa, Matti, van der Harst, Pim, Veronesi, Giovanni, Walker, Mark, Wareham, Nicholas J., Watkins, Hugh, Wichmann, H-Erich, Abecasis, Goncalo R., Assimes, Themistocles L., Berndt, Sonja I., Boehnke, Michael, Borecki, Ingrid B., Deloukas, Panos, Franke, Lude, Frayling, Timothy M., Groop, Leif C., Hunter, David J., Kaplan, Robert C., O’Connell, Jeffrey R., Qi, Lu, Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Willer, Cristen J., Visscher, Peter M., Yang, Jian, Hirschhorn, Joel N., Carola Zillikens, M., McCarthy, Mark I., Speliotes, Elizabeth K., North, Kari E., Fox, Caroline S., Barroso, Inês, Franks, Paul W., Ingelsson, Erik, Heid, Iris M., Loos, Ruth J. F., Cupples, L. Adrienne, Morris, Andrew P., Lindgren, Cecilia M., Mohlke, Karen L, Devuyst, Olivier, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Shungin, Dmitry, Winkler, Thomas W., Croteau-Chonka, Damien C., Ferreira, Teresa, Locke, Adam E., Mägi, Reedik, Strawbridge, Rona J., Pers, Tune H., Fischer, Krista, Justice, Anne E., Workalemahu, Tsegaselassie, Wu, Joseph M. W., Buchkovich, Martin L., Heard-Costa, Nancy L., Roman, Tamara S., Drong, Alexander W., Song, Ci, Gustafsson, Stefan, Day, Felix R., Esko, Tonu, Fall, Tove, Kutalik, Zoltán, Luan, Jian’an, Randall, Joshua C., Scherag, André, Vedantam, Sailaja, Wood, Andrew R., Chen, Jin, Fehrmann, Rudolf, Karjalainen, Juha, Kahali, Bratati, Liu, Ching-Ti, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bragg-Gresham, Jennifer L., Buyske, Steven, Demirkan, Ayse, Ehret, Georg B., Feitosa, Mary F., Goel, Anuj, Jackson, Anne U., Johnson, Toby, Kleber, Marcus E., Kristiansson, Kati, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Palmer, Cameron D., Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J., Prokopenko, Inga, Stančáková, Alena, Ju Sung, Yun, Tanaka, Toshiko, Teumer, Alexander, Van Vliet-Ostaptchouk, Jana V., Yengo, Loïc, Zhang, Weihua, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M., Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blüher, Matthias, Böhringer, Stefan, Bonnet, Fabrice, Böttcher, Yvonne, Bruinenberg, Marcel, Carba, Delia B., Caspersen, Ida H., Clarke, Robert, Warwick Daw, E., Deelen, Joris, Deelman, Ewa, Delgado, Graciela, Doney, Alex S. F., Eklund, Niina, Erdos, Michael R., Estrada, Karol, Eury, Elodie, Friedrich, Nele, Garcia, Melissa E., Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S., Golay, Alain, Grallert, Harald, Grammer, Tanja B., Gräßler, Jürgen, Grewal, Jagvir, Groves, Christopher J., Haller, Toomas, Hallmans, Goran, Hartman, Catharina A., Hassinen, Maija, Hayward, Caroline, Heikkilä, Kauko, Herzig, Karl-Heinz, Helmer, Quinta, Hillege, Hans L., Holmen, Oddgeir, Hunt, Steven C., Isaacs, Aaron, Ittermann, Till, James, Alan L., Johansson, Ingegerd, Juliusdottir, Thorhildur, Kalafati, Ioanna-Panagiota, Kinnunen, Leena, Koenig, Wolfgang, Kooner, Ishminder K., Kratzer, Wolfgang, Lamina, Claudia, Leander, Karin, Lee, Nanette R., Lichtner, Peter, Lind, Lars, Lindström, Jaana, Lobbens, Stéphane, Lorentzon, Mattias, Mach, François, Magnusson, Patrik K. E., Mahajan, Anubha, McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Mills, Rebecca, Moayyeri, Alireza, Monda, Keri L., Mooijaart, Simon P., Mühleisen, Thomas W., Mulas, Antonella, Müller, Gabriele, Müller-Nurasyid, Martina, Nagaraja, Ramaiah, Nalls, Michael A., Narisu, Narisu, Glorioso, Nicola, Nolte, Ilja M., Olden, Matthias, Rayner, Nigel W., Renstrom, Frida, Ried, Janina S., Robertson, Neil R., Rose, Lynda M., Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Sennblad, Bengt, Seufferlein, Thomas, Sitlani, Colleen M., Vernon Smith, Albert, Stirrups, Kathleen, Stringham, Heather M., Sundström, Johan, Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tayo, Bamidele O., Thorand, Barbara, Thorleifsson, Gudmar, Tomaschitz, Andreas, Troffa, Chiara, van Oort, Floor V. A., Verweij, Niek, Vonk, Judith M., Waite, Lindsay L., Wennauer, Roman, Wilsgaard, Tom, Wojczynski, Mary K., Wong, Andrew, Zhang, Qunyuan, Hua Zhao, Jing, Brennan, Eoin P., Choi, Murim, Eriksson, Per, Folkersen, Lasse, Franco-Cereceda, Anders, Gharavi, Ali G., Hedman, Åsa K., Hivert, Marie-France, Huang, Jinyan, Kanoni, Stavroula, Karpe, Fredrik, Keildson, Sarah, Kiryluk, Krzysztof, Liang, Liming, Lifton, Richard P., Ma, Baoshan, McKnight, Amy J., McPherson, Ruth, Metspalu, Andres, Min, Josine L., Moffatt, Miriam F., Montgomery, Grant W., Murabito, Joanne M., Nicholson, George, Nyholt, Dale R., Olsson, Christian, Perry, John R. B., Reinmaa, Eva, Salem, Rany M., Sandholm, Niina, Schadt, Eric E., Scott, Robert A., Stolk, Lisette, Vallejo, Edgar E., Westra, Harm-Jan, Zondervan, Krina T., Amouyel, Philippe, Arveiler, Dominique, Bakker, Stephan J. L., Beilby, John, Bergman, Richard N., Blangero, John, Brown, Morris J., Burnier, Michel, Campbell, Harry, Chakravarti, Aravinda, Chines, Peter S., Claudi-Boehm, Simone, Collins, Francis S., Crawford, Dana C., Danesh, John, de Faire, Ulf, de Geus, Eco J. C., Dörr, Marcus, Erbel, Raimund, Eriksson, Johan G., Farrall, Martin, Ferrannini, Ele, Ferrières, Jean, Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Gansevoort, Ron T., Gieger, Christian, Gudnason, Vilmundur, Haiman, Christopher A., Harris, Tamara B., Hattersley, Andrew T., Heliövaara, Markku, Hicks, Andrew A., Hingorani, Aroon D., Hoffmann, Wolfgang, Hofman, Albert, Homuth, Georg, Humphries, Steve E., Hyppönen, Elina, Illig, Thomas, Jarvelin, Marjo-Riitta, Johansen, Berit, Jousilahti, Pekka, Jula, Antti M., Kaprio, Jaakko, Kee, Frank, Keinanen-Kiukaanniemi, Sirkka M., Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kraja, Aldi T., Kumari, Meena, Kuulasmaa, Kari, Kuusisto, Johanna, Lakka, Timo A., Langenberg, Claudia, Le Marchand, Loic, Lehtimäki, Terho, Lyssenko, Valeriya, Männistö, Satu, Marette, André, Matise, Tara C., McKenzie, Colin A., McKnight, Barbara, Musk, Arthur W., Möhlenkamp, Stefan, Morris, Andrew D., Nelis, Mari, Ohlsson, Claes, Oldehinkel, Albertine J., Ong, Ken K., Palmer, Lyle J., Penninx, Brenda W., Peters, Annette, Pramstaller, Peter P., Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Ridker, Paul M., Ritchie, Marylyn D., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Saramies, Jouko, Sarzynski, Mark A., Schwarz, Peter E. H., Shuldiner, Alan R., Staessen, Jan A., Steinthorsdottir, Valgerdur, Stolk, Ronald P., Strauch, Konstantin, Tönjes, Anke, Tremblay, Angelo, Tremoli, Elena, Vohl, Marie-Claude, Völker, Uwe, Vollenweider, Peter, Wilson, James F., Witteman, Jacqueline C., Adair, Linda S., Bochud, Murielle, Boehm, Bernhard O., Bornstein, Stefan R., Bouchard, Claude, Cauchi, Stéphane, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Cooper, Richard S., Dedoussis, George, Ferrucci, Luigi, Froguel, Philippe, Grabe, Hans-Jörgen, Hamsten, Anders, Hui, Jennie, Hveem, Kristian, Jöckel, Karl-Heinz, Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, März, Winfried, Munroe, Patricia B., Njølstad, Inger, Oostra, Ben A., Palmer, Colin N. A., Pedersen, Nancy L., Perola, Markus, Pérusse, Louis, Peters, Ulrike, Power, Chris, Quertermous, Thomas, Rauramaa, Rainer, Rivadeneira, Fernando, Saaristo, Timo E., Saleheen, Danish, Sinisalo, Juha, Eline Slagboom, P., Snieder, Harold, Spector, Tim D., Thorsteinsdottir, Unnur, Stumvoll, Michael, Tuomilehto, Jaakko, Uitterlinden, André G., Uusitupa, Matti, van der Harst, Pim, Veronesi, Giovanni, Walker, Mark, Wareham, Nicholas J., Watkins, Hugh, Wichmann, H-Erich, Abecasis, Goncalo R., Assimes, Themistocles L., Berndt, Sonja I., Boehnke, Michael, Borecki, Ingrid B., Deloukas, Panos, Franke, Lude, Frayling, Timothy M., Groop, Leif C., Hunter, David J., Kaplan, Robert C., O’Connell, Jeffrey R., Qi, Lu, Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Willer, Cristen J., Visscher, Peter M., Yang, Jian, Hirschhorn, Joel N., Carola Zillikens, M., McCarthy, Mark I., Speliotes, Elizabeth K., North, Kari E., Fox, Caroline S., Barroso, Inês, Franks, Paul W., Ingelsson, Erik, Heid, Iris M., Loos, Ruth J. F., Cupples, L. Adrienne, Morris, Andrew P., Lindgren, Cecilia M., Mohlke, Karen L, and Devuyst, Olivier

Published
2015

437. Frequent somatic reversion of KRT1 mutations in ichthyosis with confetti.

Author

Choate, Keith A, Choate, Keith A, Lu, Yin, Zhou, Jing, Elias, Peter M, Zaidi, Samir, Paller, Amy S, Farhi, Anita, Nelson-Williams, Carol, Crumrine, Debra, Milstone, Leonard M, Lifton, Richard P, Choate, Keith A, Choate, Keith A, Lu, Yin, Zhou, Jing, Elias, Peter M, Zaidi, Samir, Paller, Amy S, Farhi, Anita, Nelson-Williams, Carol, Crumrine, Debra, Milstone, Leonard M, and Lifton, Richard P

Abstract

Widespread reversion of genetic disease is rare; however, such events are particularly evident in some skin disorders in which normal clones develop on a background of affected skin. We previously demonstrated that mutations in keratin 10 (KRT10) cause ichthyosis with confetti (IWC), a severe dominant disorder that is characterized by progressive development of hundreds of normal skin spots via revertant mosaicism. Here, we report on a clinical and histological IWC subtype in which affected subjects have red, scaly skin at birth, experience worsening palmoplantar keratoderma in childhood, and develop hundreds of normal skin spots, beginning at around 20 years of age, that increase in size and number over time. We identified a causal de novo mutation in keratin 1 (KRT1). Similar to IWC-causing KRT10 mutations, this mutation in KRT1 resulted in a C-terminal frameshift, replacing 22 C-terminal amino acids with an alternate 30-residue peptide. Mutant KRT1 caused partial collapse of the cytoplasmic intermediate filament network and mislocalized to the nucleus. As with KRT10 mutations causing IWC, reversion of KRT1 mutations occurred via mitotic recombination. Because reversion is not observed with other disease-causing keratin mutations, the results of this study implicate KRT1 and KRT10 C-terminal frameshift mutations in the high frequency of revertant mosaicism in IWC.

Published
2015

438. DCDC2 mutations cause a renal-hepatic ciliopathy by disrupting Wnt signaling

Author

Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, Circulatory Health, Schueler, Markus, Braun, Daniela A, Chandrasekar, Gayathri, Gee, Heon Yung, Klasson, Timothy D., Halbritter, Jan, Bieder, Andrea, Porath, Jonathan D, Airik, Rannar, Zhou, Weibin, LoTurco, Joseph J, Che, Alicia, Otto, Edgar A, Böckenhauer, Detlef, Sebire, Neil J, Honzik, Tomas, Harris, Peter C, Koon, Sarah J, Gunay-Aygun, Meral, Saunier, Sophie, Zerres, Klaus, Bruechle, Nadina Ortiz, Drenth, Joost P H, Pelletier, Laurence, Tapia-Páez, Isabel, Lifton, Richard P, Giles, R, Kere, Juha, Hildebrandt, Friedhelm, Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, Circulatory Health, Schueler, Markus, Braun, Daniela A, Chandrasekar, Gayathri, Gee, Heon Yung, Klasson, Timothy D., Halbritter, Jan, Bieder, Andrea, Porath, Jonathan D, Airik, Rannar, Zhou, Weibin, LoTurco, Joseph J, Che, Alicia, Otto, Edgar A, Böckenhauer, Detlef, Sebire, Neil J, Honzik, Tomas, Harris, Peter C, Koon, Sarah J, Gunay-Aygun, Meral, Saunier, Sophie, Zerres, Klaus, Bruechle, Nadina Ortiz, Drenth, Joost P H, Pelletier, Laurence, Tapia-Páez, Isabel, Lifton, Richard P, Giles, R, Kere, Juha, and Hildebrandt, Friedhelm

Published
2015

439. Mutations of the SLIT2–ROBO2 pathway genes SLIT2 and SRGAP1 confer risk for congenital anomalies of the kidney and urinary tract

Author

Genetica Klinische Genetica, Child Health, Genetica Groep Van Tintelen, Hwang, Daw Yang, Kohl, Stefan, Fan, Xueping, Vivante, Asaf, Chan, Stefanie, Dworschak, Gabriel C., Schulz, Julian, van Eerde, Albertien M., Hilger, Alina C., Gee, Heon Yung, Pennimpede, Tracie, Herrmann, Bernhard G., van de Hoek, Glenn, Renkema, Kirsten Y., Schell, Christoph, Huber, Tobias B., Reutter, Heiko M., Soliman, Neveen A., Stajic, Natasa, Bogdanovic, Radovan, Kehinde, Elijah O., Lifton, Richard P., Tasic, Velibor, Lu, Weining, Hildebrandt, Friedhelm, Genetica Klinische Genetica, Child Health, Genetica Groep Van Tintelen, Hwang, Daw Yang, Kohl, Stefan, Fan, Xueping, Vivante, Asaf, Chan, Stefanie, Dworschak, Gabriel C., Schulz, Julian, van Eerde, Albertien M., Hilger, Alina C., Gee, Heon Yung, Pennimpede, Tracie, Herrmann, Bernhard G., van de Hoek, Glenn, Renkema, Kirsten Y., Schell, Christoph, Huber, Tobias B., Reutter, Heiko M., Soliman, Neveen A., Stajic, Natasa, Bogdanovic, Radovan, Kehinde, Elijah O., Lifton, Richard P., Tasic, Velibor, Lu, Weining, and Hildebrandt, Friedhelm

Published
2015

440. Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy

Author

Goh, Gerald, primary, Walradt, Trent, additional, Markarov, Vladimir, additional, Blom, Astrid, additional, Riaz, Nadeem, additional, Doumani, Ryan, additional, Stafstrom, Krista, additional, Moshiri, Ata, additional, Yelistratova, Lola, additional, Levinsohn, Jonathan, additional, Chan, Timothy A., additional, Nghiem, Paul, additional, Lifton, Richard P., additional, and Choi, Jaehyuk, additional

Published
2015
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441. De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies

Author

Homsy, Jason, primary, Zaidi, Samir, additional, Shen, Yufeng, additional, Ware, James S., additional, Samocha, Kaitlin E., additional, Karczewski, Konrad J., additional, DePalma, Steven R., additional, McKean, David, additional, Wakimoto, Hiroko, additional, Gorham, Josh, additional, Jin, Sheng Chih, additional, Deanfield, John, additional, Giardini, Alessandro, additional, Porter, George A., additional, Kim, Richard, additional, Bilguvar, Kaya, additional, López-Giráldez, Francesc, additional, Tikhonova, Irina, additional, Mane, Shrikant, additional, Romano-Adesman, Angela, additional, Qi, Hongjian, additional, Vardarajan, Badri, additional, Ma, Lijiang, additional, Daly, Mark, additional, Roberts, Amy E., additional, Russell, Mark W., additional, Mital, Seema, additional, Newburger, Jane W., additional, Gaynor, J. William, additional, Breitbart, Roger E., additional, Iossifov, Ivan, additional, Ronemus, Michael, additional, Sanders, Stephan J., additional, Kaltman, Jonathan R., additional, Seidman, Jonathan G., additional, Brueckner, Martina, additional, Gelb, Bruce D., additional, Goldmuntz, Elizabeth, additional, Lifton, Richard P., additional, Seidman, Christine E., additional, and Chung, Wendy K., additional

Published
2015
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442. Genes and environment in neonatal intraventricular hemorrhage

Author

Ment, Laura R., primary, Ådén, Ulrika, additional, Bauer, Charles R., additional, Bada, Henrietta S., additional, Carlo, Waldemar A., additional, Kaiser, Jeffrey R., additional, Lin, Aiping, additional, Cotten, Charles Michael, additional, Murray, Jeffrey, additional, Page, Grier, additional, Hallman, Mikko, additional, Lifton, Richard P., additional, and Zhang, Heping, additional

Published
2015
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443. CELA2Amutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation

Author

Esteghamat, Fatemehsadat, Broughton, James, Smith, Emily, Cardone, Rebecca, Tyagi, Tarun, Guerra, Mateus, Szabó, András, Ugwu, Nelson, Mani, Mitra, Azari, Bani, Kayingo, Gerald, Chung, Sunny, Fathzadeh, Mohsen, Weiss, Ephraim, Bender, Jeffrey, Mane, Shrikant, Lifton, Richard, Adeniran, Adebowale, Nathanson, Michael, Gorelick, Fred, Hwa, John, Sahin-Tóth, Miklós, Belfort-DeAguiar, Renata, Kibbey, Richard, and Mani, Arya

Abstract

Factors that underlie the clustering of metabolic syndrome traits are not fully known. We performed whole-exome sequence analysis in kindreds with extreme phenotypes of early-onset atherosclerosis and metabolic syndrome, and identified novel loss-of-function mutations in the gene encoding the pancreatic elastase chymotrypsin-like elastase family member 2A (CELA2A). We further show that CELA2A is a circulating enzyme that reduces platelet hyperactivation, triggers both insulin secretion and degradation, and increases insulin sensitivity. CELA2A plasma levels rise postprandially and parallel insulin levels in humans. Loss of these functions by the mutant proteins provides insight into disease mechanisms and suggests that CELA2A could be an attractive therapeutic target. Exome sequencing identifies loss-of-function CELA2Amutations in families with early-onset atherosclerosis and metabolic syndrome. Functional studies show that CELA2A is a circulating enzyme that reduces platelet activation, triggers insulin secretion and degradation, and increases insulin sensitivity.

Published
2019
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444. Mutations in PERPCause Dominant and Recessive Keratoderma

Author

Duchatelet, Sabine, Boyden, Lynn M., Ishida-Yamamoto, Akemi, Zhou, Jing, Guibbal, Laure, Hu, Ronghua, Lim, Young H., Bole-Feysot, Christine, Nitschké, Patrick, Santos-Simarro, Fernando, de Lucas, Raul, Milstone, Leonard M., Gildenstern, Vanessa, Helfrich, Yolanda R., Attardi, Laura D., Lifton, Richard P., Choate, Keith A., and Hovnanian, Alain

Abstract

Investigation of genetic determinants of Mendelian skin disorders has substantially advanced understanding of epidermal biology. Here we show that mutations in PERP, encoding a crucial component of desmosomes, cause both dominant and recessive human keratoderma. Heterozygosity for a C-terminal truncation, which produces a protein that appears to be unstably incorporated into desmosomes, causes Olmsted syndrome with severe periorificial and palmoplantar keratoderma in multiple unrelated kindreds. Homozygosity for an N-terminal truncation ablates expression and causes widespread erythrokeratoderma, with expansion of epidermal differentiation markers. Both exhibit epidermal hyperproliferation, immature desmosomes lacking a dense midline observed via electron microscopy, and impaired intercellular adhesion upon mechanical stress. Localization of other desmosomal components appears normal, which is in contrast to other conditions caused by mutations in genes encoding desmosomal proteins. These discoveries highlight the essential role of PERPin human desmosomes and epidermal homeostasis and further expand the heterogeneous spectrum of inherited keratinization disorders.

Published
2019
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446. Genetic landscape of metastatic and recurrent head and neck squamous cell carcinoma

Author

Hedberg, Matthew L., primary, Goh, Gerald, additional, Chiosea, Simion I., additional, Bauman, Julie E., additional, Freilino, Maria L., additional, Zeng, Yan, additional, Wang, Lin, additional, Diergaarde, Brenda B., additional, Gooding, William E., additional, Lui, Vivian W.Y., additional, Herbst, Roy S., additional, Lifton, Richard P., additional, and Grandis, Jennifer R., additional

Published
2015
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447. Low-levelAPCmutational mosaicism is the underlying cause in a substantial fraction of unexplained colorectal adenomatous polyposis cases

Author

Spier, Isabel, primary, Drichel, Dmitriy, additional, Kerick, Martin, additional, Kirfel, Jutta, additional, Horpaopan, Sukanya, additional, Laner, Andreas, additional, Holzapfel, Stefanie, additional, Peters, Sophia, additional, Adam, Ronja, additional, Zhao, Bixiao, additional, Becker, Tim, additional, Lifton, Richard P, additional, Perner, Sven, additional, Hoffmann, Per, additional, Kristiansen, Glen, additional, Timmermann, Bernd, additional, Nöthen, Markus M, additional, Holinski-Feder, Elke, additional, Schweiger, Michal R, additional, and Aretz, Stefan, additional

Published
2015
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448. Dominantde novo DSPmutations cause erythrokeratodermia-cardiomyopathy syndrome

Author

Boyden, Lynn M., primary, Kam, Chen Y., additional, Hernández-Martín, Angela, additional, Zhou, Jing, additional, Craiglow, Brittany G., additional, Sidbury, Robert, additional, Mathes, Erin F., additional, Maguiness, Sheilagh M., additional, Crumrine, Debra A., additional, Williams, Mary L., additional, Hu, Ronghua, additional, Lifton, Richard P., additional, Elias, Peter M., additional, Green, Kathleen J., additional, and Choate, Keith A., additional

Published
2015
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449. Absence ofKMT2D/MLL2mutations in abdominal paraganglioma

Author

Stenman, Adam, primary, Juhlin, Carl C., additional, Haglund, Felix, additional, Brown, Taylor C., additional, Clark, Victoria E., additional, Svahn, Fredrika, additional, Bilguvar, Kaya, additional, Goh, Gerald, additional, Korah, Reju, additional, Lifton, Richard P., additional, and Carling, Tobias, additional

Published
2015
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450. The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities

Author

Chong, Jessica X., primary, Buckingham, Kati J., additional, Jhangiani, Shalini N., additional, Boehm, Corinne, additional, Sobreira, Nara, additional, Smith, Joshua D., additional, Harrell, Tanya M., additional, McMillin, Margaret J., additional, Wiszniewski, Wojciech, additional, Gambin, Tomasz, additional, Coban Akdemir, Zeynep H., additional, Doheny, Kimberly, additional, Scott, Alan F., additional, Avramopoulos, Dimitri, additional, Chakravarti, Aravinda, additional, Hoover-Fong, Julie, additional, Mathews, Debra, additional, Witmer, P. Dane, additional, Ling, Hua, additional, Hetrick, Kurt, additional, Watkins, Lee, additional, Patterson, Karynne E., additional, Reinier, Frederic, additional, Blue, Elizabeth, additional, Muzny, Donna, additional, Kircher, Martin, additional, Bilguvar, Kaya, additional, López-Giráldez, Francesc, additional, Sutton, V. Reid, additional, Tabor, Holly K., additional, Leal, Suzanne M., additional, Gunel, Murat, additional, Mane, Shrikant, additional, Gibbs, Richard A., additional, Boerwinkle, Eric, additional, Hamosh, Ada, additional, Shendure, Jay, additional, Lupski, James R., additional, Lifton, Richard P., additional, Valle, David, additional, Nickerson, Deborah A., additional, and Bamshad, Michael J., additional

Published
2015
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