Clinical, Molecular, and Cellular Features of Non-Puerto Rican Hermansky–Pudlak Syndrome Patients of Hispanic Descent Carmelo Carmona-Rivera, Gretchen.

Slides:

Advertisements

Similar presentations

Amy M. Dworkin, Stephanie Y. Tseng, Dawn C. Allain, O

Advertisements

Volume 117, Issue 1, Pages (January 2000)

A Novel XPA Gene Mutation and its Functional Analysis in a Japanese Patient with Xeroderma Pigmentosum Group A Miki Tanioka, Arief Budiyant, Takahiro.

Epidermolysis Bullosa: Novel and De Novo Premature Termination Codon and Deletion Mutations in the Plectin Gene Predict Late-Onset Muscular Dystrophy

Next-Generation Sequencing for Mutation Detection in Heritable Skin Diseases: The Paradigm of Pseudoxanthoma Elasticum Andrew P. South, Qiaoli Li, Jouni.

Melanocytes Derived from Patients with Hermansky–Pudlak Syndrome Types 1, 2, and 3 Have Distinct Defects in Cargo Trafficking Bonnie Richmond, Marjan.

Next-Generation Sequencing: Methodology and Application

Eija Siintola, Meral Topcu, Nina Aula, Hannes Lohi, Berge A

Sirolimus-Associated Diffuse Alveolar Hemorrhage

Genomic Amplification of the Human Plakophilin 1 Gene and Detection of a New Mutation in Ectodermal Dysplasia/Skin Fragility Syndrome Neil V. Whittock,

Aoi Nakano, Hajime Nakano, Sal LaForgia, Leena Pulkkinen, Jouni Uitto

Natural Gene Therapy May Occur in All Patients with Generalized Non-Herlitz Junctional Epidermolysis Bullosa with COL17A1 Mutations Anna M.G. Pasmooij,

Abnormal Translocation of Tyrosinase and Tyrosinase-Related Protein 1 in Cutaneous Melanocytes of Hermansky–Pudlak Syndrome and in Melanoma Cells Transfected.

Exome Sequencing Identifies SLC24A5 as a Candidate Gene for Nonsyndromic Oculocutaneous Albinism Ai-Hua Wei, Dong-Jie Zang, Zhe Zhang, Xuan-Zhu Liu,

Kinesin and Kinectin Can Associate with the Melanosomal Surface and Form a Link with Microtubules in Normal Human Melanocytes1 Garnet Vancoillie, Jo.

Colocalization of Kindlin-1, Kindlin-2, and Migfilin at Keratinocyte Focal Adhesion and Relevance to the Pathophysiology of Kindler Syndrome J.E. Lai-Cheong,

Zebrafish: A Model System to Study Heritable Skin Diseases

Epidermolysis Bullosa: Novel and De Novo Premature Termination Codon and Deletion Mutations in the Plectin Gene Predict Late-Onset Muscular Dystrophy

Epididymal Cysteine-Rich Secretory Protein 1 Encoding Gene Is Expressed in Murine Hair Follicles and Downregulated in Mice Overexpressing Hoxc13 Ron.

Mild Recessive Bullous Congenital Ichthyosiform Erythroderma due to a Previously Unidentified Homozygous Keratin 10 Nonsense Mutation Akiko Tsubota,

Analysis of Rare APC Variants at the mRNA Level

Merkel Cell Polyomavirus–Positive Merkel Cell Carcinoma Requires Viral Small T- Antigen for Cell Proliferation Masahiro Shuda, Yuan Chang, Patrick S.

Identification and Rescue of Splice Defects Caused by Two Neighboring Deep-Intronic ABCA4 Mutations Underlying Stargardt Disease Silvia Albert, Alejandro.

Splice Site and Deletion Mutations in Keratin (KRT1 and KRT10) Genes: Unusual Phenotypic Alterations in Scandinavian Patients with Epidermolytic Hyperkeratosis

Novel Homozygous and Compound Heterozygous COL17A1 Mutations Associated with Junctional Epidermolysis Bullosa Michaela Floeth, Heike Schäcke, Nadja Hammami-Hauasli,

Mutation in PIGA Results in a CD52-Negative Escape Variant in a Sézary Syndrome Patient during Alemtuzumab Treatment Constantijn J.M. Halkes, Willem.

A Rare Case of Hypohidrotic Ectodermal Dysplasia Caused by Compound Heterozygous Mutations in the EDAR Gene Yutaka Shimomura, Nobuyuki Sato, Akinori.

Cycloheximide Facilitates the Identification of Aberrant Transcripts Resulting from a Novel Splice-Site Mutation in COL17A1 in a Patient with Generalized.

Activation of a Cryptic Splice Site of PTEN and Loss of Heterozygosity in Benign Skin Lesions in Cowden Disease Stephen J. Meltzer, Manfred Wolter Journal.

Neurofibromatosis Type 1 Protein and Amyloid Precursor Protein Interact in Normal Human Melanocytes and Colocalize with Melanosomes Sofie De Schepper,

Cryptic Splicing at a Non-Consensus Splice-Donor in a Patient with a Novel Mutation in the Plakophilin-1 Gene Peter M. Steijlen, Maurice A.M. van Steensel,

Detection of a Peripheral Blood T Cell Clone is an Independent Prognostic Marker in Mycosis Fungoides Elisabeth A. Fraser-Andrews, Alison J. Woolford,

H. Randolph Byers, Mina Yaar, Mark S. Eller, Nicole L

A Homozygous Nonsense Mutation in Type XVII Collagen Gene (COL17A1) Uncovers an Alternatively Spliced mRNA Accounting for an Unusually Mild Form of Non-Herlitz.

Nadeem Hussain, Martha Quezado, Marjan Huizing, David Geho, James G

Senator Hazelwood, Vorasuk Shotelersuk, Scott C

A Novel XPA Gene Mutation and its Functional Analysis in a Japanese Patient with Xeroderma Pigmentosum Group A Miki Tanioka, Arief Budiyant, Takahiro.

The Thinning Top: Why Old People Have Less Hair

The Melanocortin 5 Receptor is Expressed in Human Sebaceous Glands and Rat Preputial Cells Diane Thiboutot, Aruntha Sivarajah, Kathryn Gilliland, Zhaoyuan.

Founder Mutations in the Lipase H Gene in Families with Autosomal Recessive Woolly Hair/Hypotrichosis Yutaka Shimomura, Muhammad Wajid, Abraham Zlotogorski,

Cellular Defects in Chediak–Higashi Syndrome Correlate with the Molecular Genotype and Clinical Phenotype Wendy Westbroek, David Adams, Marjan Huizing,

Clinical Snippets Journal of Investigative Dermatology

Minutes of the Board of Directors Meeting

Lack of EVER2 Protein in Two Epidermodysplasia Verruciformis Patients with Skin Cancer Presenting Previously Unreported Homozygous Genetic Deletions in.

High Frequency of Hermansky–Pudlak Syndrome Type 1 (HPS1) Among Japanese Albinism Patients and Functional Analysis of HPS1 Mutant Protein Shiro Ito,

Homozygous Mutations in the 5′ Region of the JUP Gene Result in Cutaneous Disease but Normal Heart Development in Children Rita M. Cabral, Lu Liu, Carol.

Journal of Investigative Dermatology

Transcriptional Profiling of Psoriasis Using RNA-seq Reveals Previously Unidentified Differentially Expressed Genes Ali Jabbari, Mayte Suárez-Fariñas,

Society for Investigative Dermatology 2010 Meeting Minutes

A New Mouse Model of Junctional Epidermolysis Bullosa: The LAMB3 628G>A Knockin Mouse Johanna Hammersen, Jin Hou, Stephanie Wünsche, Sven Brenner, Thomas.

Assessing the Functional Characteristics of Synonymous and Nonsynonymous Mutation Candidates by Use of Large DNA Constructs A.M. Eeds, D. Mortlock, R.

Revertant Mosaicism in Recessive Dystrophic Epidermolysis Bullosa

Research Snippets Journal of Investigative Dermatology

Ultrastructural Features of Trafficking Defects Are Pronounced in Melanocytic Nevus in Hermansky–Pudlak Syndrome Type 1 Ken Natsuga, Masashi Akiyama,

Compound Heterozygosity for Novel Splice Site Mutations in the BPAG2/COL17A1 Gene Underlies Generalized Atrophic Benign Epidermolysis Bullosa Leena Pulkkinen,

A Novel Gene Expressed in Human Keratinocytes with Long-Term In Vitro Growth Potential is Required for Cell Growth Laure Aurelian, Cynthia C. Smith,

Fetal Microchimerism Is Common in Normal and Diseased Vulvar Skin

Wook Lew Journal of Investigative Dermatology

Human Natural Killer T Cells Infiltrate into the Skin at Elicitation Sites of Allergic Contact Dermatitis Michael D. Gober, Rita Fishelevich, Yuming.

Identification of Transglutaminase 3 Splicing Isoforms

Expression of Opsin Molecule in Cultured Murine Melanocyte

Intronic ITGA3 Mutation Impacts Splicing Regulation and Causes Interstitial Lung Disease, Nephrotic Syndrome, and Epidermolysis Bullosa Yinghong He,

Identification of Skn-1n, a Splice Variant Induced by High Calcium Concentration and Specifically Expressed in Normal Human Keratinocytes Koji Nakajima,

Homozygosity Mapping and Whole-Exome Sequencing to Detect SLC45A2 and G6PC3 Mutations in a Single Patient with Oculocutaneous Albinism and Neutropenia

Cerebral Cavernomas in a Family with Multiple Cutaneous and Uterine Leiomyomas Associated with a New Mutation in the Fumarate Hydratase Gene Elena Campione,

A Second Leaky Splice-Site Mutation in the Spastin Gene

Marcel F. Jonkman, Prof. Dr, Hendri H

Genetic Heterogeneity of KID Syndrome: Identification of a Cx30 Gene (GJB6) Mutation in a Patient with KID Syndrome and Congenital Atrichia Amy Y. Jan,

Hermansky-Pudlak Syndrome Type 3 in Ashkenazi Jews and Other Non–Puerto Rican Patients with Hypopigmentation and Platelet Storage-Pool Deficiency Marjan.

Exon Skipping in IVD RNA Processing in Isovaleric Acidemia Caused by Point Mutations in the Coding Region of the IVD Gene Jerry Vockley, Peter K. Rogan,

Presentation transcript:

Clinical, Molecular, and Cellular Features of Non-Puerto Rican Hermansky–Pudlak Syndrome Patients of Hispanic Descent Carmelo Carmona-Rivera, Gretchen Golas, Richard A. Hess, Nicholas D. Cardillo, Elijah H. Martin, Kevin O'Brien, Ekaterini Tsilou, Bernadette R. Gochuico, James G. White, Marjan Huizing, William A. Gahl Journal of Investigative Dermatology Volume 131, Issue 12, Pages 2394-2400 (December 2011) DOI: 10.1038/jid.2011.228 Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Clinical and molecular findings among non-Puerto Rican Hispanic Hermansky–Pudlak syndrome (HPS) patients. (a) Pigmentation and sequencing chromatograms of all six patients reported in this study. All patients showed hypopigmented skin with hair colors ranging from blond to brown. (b) Representative images of iris transillumination (in HPS117-1) and pale fundus (in HPS118-1), compared with controls (Ctrl). Journal of Investigative Dermatology 2011 131, 2394-2400DOI: (10.1038/jid.2011.228) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Hallmarks of Hermansky–Pudlak syndrome (HPS) patients. (a) Representative whole-mount (top panel) and transmission (bottom panel) electron microscope images of selected patients compared with controls (Ctrl), showing an absence of platelet delta granules (arrows in control images). (b) Conventional chest computed tomography (CT) of HPS117-1 (top image) shows diffuse bilateral peripheral interstitial pulmonary infiltrates (arrows). A CT scan from HPS118-1 (middle image) shows mild bilateral interstitial opacities (arrows) predominantly in subpleural areas. In contrast, no pulmonary infiltrates were found on a CT scan from HPS361-1 (bottom image), who is a 22-year-old man with HPS-1 and no lung disease. Journal of Investigative Dermatology 2011 131, 2394-2400DOI: (10.1038/jid.2011.228) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Immunoblot analysis of patients' fibroblast extracts. Immunoblotting was performed with antibodies against Hermansky–Pudlak syndrome (HPS)4 (to detect BLOC-3 defects), HPS5 (to detect BLOC-2 defects), and α-tubulin (loading control). (a) Normal, HPS-3, and HPS-1 fibroblast extracts were loaded as controls (lanes 1–3) and compared with the patients' protein expression. Patient HPS117-1 showed decreased HPS4 expression, similar to that of control HPS-1 cells (lane 3), suggesting an HPS-1 defect. Patients HPS125-5 and HPS353-5 expressed no HPS5 protein, confirming an HPS-5 defect. Patient HPS150-4 expressed no HPS4 protein, confirming an HPS-4 defect. (b) Patient HPS163-1 showed reduced levels of HPS4 protein, similar to the HPS-1 loading control (lane 1), suggesting HPS-1 disease in this patient. Journal of Investigative Dermatology 2011 131, 2394-2400DOI: (10.1038/jid.2011.228) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Complementary DNA (cDNA) analysis of patient HPS353-5. (a) Schematic representation of the HPS5 gene and location of the primers used for PCR analysis to detect splice-site alteration in patient HPS353-5. The patient's splice-site variant c.1,634+1G>A (intron 13) is located 1-bp intronic from the exon12–exon13 boundary (asterisk). (b) cDNA amplification of exons 11–16 of the HPS5 cDNA transcript showing the expected band of 694 bp and a lower-molecular-weight band around 570 bp. (c) Sequence analysis of the lower-molecular-weight band revealed skipping of exon 13 (124-bp) in patient HPS353-5, confirming the pathogenicity of the new HPS5 splice-site variant in this patient. Journal of Investigative Dermatology 2011 131, 2394-2400DOI: (10.1038/jid.2011.228) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions