Genetic Reversion via Mitotic Recombination in Ichthyosis with Confetti due to a KRT10 Polyalanine Frameshift Mutation Young H. Lim, Jingyao Qiu, Corey.

Slides:

Advertisements

Similar presentations

Identification of a Novel Locus Associated with Congenital Recessive Ichthyosis on 12p11.2–q13 Mordechai Mizrachi-Koren, Dan Geiger, Margarita Indelman,

Advertisements

Maik Dahlhoff, Sukalp Muzumdar, Matthias Schäfer, Marlon R. Schneider

A Novel Mutation and Large Size Polymorphism Affecting the V2 Domain of Keratin 1 in an African-American Family with Severe, Diffuse Palmoplantar Keratoderma.

Abnormal Transglutaminase 1 Expression Pattern in a Subset of Patients with Erythrodermic Autosomal Recessive Ichthyosis Keith A. Choate, Paul A. Khavari

Young H. Lim, Jonathan M. Fisher, Marcus W. Bosenberg, Keith A

Gene-Targeted Next Generation Sequencing Identifies PNPLA1 Mutations in Patients with a Phenotypic Spectrum of Autosomal Recessive Congenital Ichthyosis:

Transient Bullous Dermolysis of the Newborn Associated with Compound Heterozygosity for Recessive and Dominant COL7A1 Mutations Nadja Hammami-Hauasli,

Identification of a Novel Mutation and a De Novo Mutation in DKC1 in Two Chinese Pedigrees with Dyskeratosis Congenita Ying-guo Ding, Tie-shan Zhu, Wei.

Ectodysplasin A Pathway Contributes to Human and Murine Skin Repair

Mutations in the Keratin 85 (KRT85/hHb5) Gene Underlie Pure Hair and Nail Ectodermal Dysplasia Yutaka Shimomura, Muhammad Wajid, Mazen Kurban, Nobuyuki.

A Child with Epidermolytic Ichthyosis from a Parent with Epidermolytic Nevus: Risk Evaluation of Transmission from Mosaic to Germline Michihiro Kono,

Severe Palmo-Plantar Hyperkeratosis in Dowling–Meara Epidermolysis Bullosa Simplex Caused by a Mutation in the Keratin 14 Gene (KRT14) Carrie S. Shemanko

Somatic Mutations in NEK9 Cause Nevus Comedonicus

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

Anna M. G. Pasmooij, Hendri H. Pas, Franciska C. L

Inflammatory Linear Verrucous Epidermal Nevus with a Postzygotic GJA1 Mutation Is a Mosaic Erythrokeratodermia Variabilis et Progressiva Noriko Umegaki-Arao,

Transcription Factor MafB Coordinates Epidermal Keratinocyte Differentiation Masashi Miyai, Michito Hamada, Takashi Moriguchi, Junichiro Hiruma, Akiyo.

Christina A. Young, Richard L

Marcel F. Jonkman, Anna M. G. Pasmooij, Suzanne G. M. A

Single Amino Acid Deletion in Kindlin-1 Results in Partial Protein Degradation Which Can Be Rescued by Chaperone Treatment Kristin Maier, Yinghong He,

Clinical Snippets Journal of Investigative Dermatology

Fusako Sato, Gyula Soos, Charles Link, Kenzo Sato

Efrat Avigad Laron, Emil Aamar, David Enshell-Seijffers

Skin-Specific Deletion of Mis18α Impedes Proliferation and Stratification of Epidermal Keratinocytes Koog Chan Park, Minkyoung Lee, Yoon Jeon, Raok Jeon,

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

Foxc1 Ablated Mice Are Anhidrotic and Recapitulate Features of Human Miliaria Sweat Retention Disorder Chang-Yi Cui, Ryuga Ishii, Dean P. Campbell, Marc.

Revertant Mosaicism in Ichthyosis with Confetti Caused by a Frameshift Mutation in KRT1 Shotaro Suzuki, Toshifumi Nomura, Toshinari Miyauchi, Masae Takeda,

Anna M. G. Pasmooij, Hendri H. Pas, Franciska C. L

Genetic Heterogeneity in Erythrokeratodermia Variabilis: Novel Mutations in the Connexin Gene GJB4 (Cx30.3) and Genotype-Phenotype Correlations Gabriele.

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

NRAS, NRAS, Which Mutation Is Fairest of Them All?

Refined Mapping of Naegeli–Franceschetti– Jadassohn Syndrome to a 6 cM Interval on Chromosome 17q11.2-q21 and Investigation of Candidate Genes Eli Sprecher,

High Frequency of Loss of Heterozygosity on Chromosome Region 9p21–p22 but Lack of p16INK4a/p19ARF Mutations in Greek Patients with Basal Cell Carcinoma.

Mutations Affecting Keratin 10 Surface-Exposed Residues Highlight the Structural Basis of Phenotypic Variation in Epidermolytic Ichthyosis Haris Mirza,

Semidominant Inheritance in Epidermolytic Ichthyosis

Acral Peeling Skin Syndrome with TGM5 Gene Mutations May Resemble Epidermolysis Bullosa Simplex in Young Individuals Dimitra Kiritsi, Ioana Cosgarea,

Establishment of Two Mouse Models for CEDNIK Syndrome Reveals the Pivotal Role of SNAP29 in Epidermal Differentiation Stina A. Schiller, Christina Seebode,

Fibroblast-Derived Clusterin Negatively Regulates Pigmentation

Postzygotic Mutations in Beta-Actin Are Associated with Becker’s Nevus and Becker’s Nevus Syndrome Emily D. Cai, Bryan K. Sun, Audris Chiang, Anna Rogers,

A Novel Helix Termination Mutation in Keratin 10 in Annular Epidermolytic Ichthyosis, a Variant of Bullous Congenital Ichthyosiform Erythroderma Yasushi.

Recessive Epidermolytic Hyperkeratosis Caused by a Previously Unreported Termination Codon Mutation in the Keratin 10 Gene Patrick Terheyden, Gundula.

Heterozygous Null Alleles in Filaggrin Contribute to Clinical Dry Skin in Young Adults and the Elderly Ann Sergeant, Linda E. Campbell, Peter R. Hull,

Guofang Hu, Meltem Önder, Melissa Gill, Burhan Aksakal, Murat Öztas, M

Compound Heterozygous TGM1 Mutations Including a Novel Missense Mutation L204Q in a Mild Form of Lamellar Ichthyosis Masashi Akiyama, Itsuro Matsuo

Activating HRAS Mutation in Nevus Spilus

Pathogenesis-Based Therapy Reverses Cutaneous Abnormalities in an Inherited Disorder of Distal Cholesterol Metabolism Amy S. Paller, Maurice A.M. van.

A Heterozygous Frameshift Mutation in the V1 Domain of Keratin 5 in a Family with Dowling–Degos Disease Haihui Liao, Yiwei Zhao, David U. Baty, John.

Autosomal-Dominant Woolly Hair Resulting from Disruption of Keratin 74 (KRT74), a Potential Determinant of Human Hair Texture Yutaka Shimomura, Muhammad.

Epidermodysplasia Verruciformis: Genetic Heterogeneity and EVER1 and EVER2 Mutations Revealed by Genome-Wide Analysis Leila Youssefian, Hassan Vahidnezhad,

A Missense Mutation in TGM5 Causes Acral Peeling Skin Syndrome in a Tunisian Family Monia Kharfi, Nadia El Fekih, Donia Ammar, Habib Jaafoura, Susanne.

IL-17 Takes Center Stage in Dermatophytosis

Loss of Normal Profilaggrin and Filaggrin in Flaky Tail (ft/ft) Mice: an Animal Model for the Filaggrin-Deficient Skin Disease Ichthyosis Vulgaris Richard.

Rebecca M. Porter, Julia Reichelt, Declan P. Lunny, Thomas M. Magin, E

Journal of Investigative Dermatology

Mutations in the Desmoglein 4 Gene Underlie Localized Autosomal Recessive Hypotrichosis with Monilethrix Hairs and Congenital Scalp Erosions Julie V.

Epidermolytic Hyperkeratosis and Epidermolysis Bullosa Simplex Caused by Frameshift Mutations Altering the V2 Tail Domains of Keratin 1 and Keratin 5

MYD88 Somatic Mutation Is a Genetic Feature of Primary Cutaneous Diffuse Large B- Cell Lymphoma, Leg Type Anne Pham-Ledard, David Cappellen, Fabian Martinez,

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

A Usual Frameshift and Delayed Termination Codon Mutation in Keratin 5 Causes a Novel Type of Epidermolysis Bullosa Simplex with Migratory Circinate Erythema

Overexpression of Wild-type p53 in Lichen Sclerosus adjacent to Human Papillomavirus-negative Vulvar Cancer Katrina Vanin, James Scurry, Heather Thorne,

Journal of Investigative Dermatology

Alterations in Desmosome Size and Number Coincide with the Loss of Keratinocyte Cohesion in Skin with Homozygous and Heterozygous Defects in the Desmosomal.

Frances J.D. Smith, W.H. Irwin McLean

A Mutation in the V1 Domain of K16 is Responsible for Unilateral Palmoplantar Verrucous Nevus Alessandro Terrinoni, Vincenzo De Laurenzi, Eleonora Candi,

Neil V. Whittock, Frances J. Smith, W.H. Irwin McLean

Truncation of CGI-58 Protein Causes Malformation of Lamellar Granules Resulting in Ichthyosis in Dorfman-Chanarin Syndrome Masashi Akiyama, Daisuke Sawamura,

Novel ALDH3A2 Heterozygous Mutations Are Associated with Defective Lamellar Granule Formation in a Japanese Family of Sjögren–Larsson Syndrome Akihiko.

Journal of Investigative Dermatology

Novel Keratin 14 Mutations in Patients with Severe Recessive Epidermolysis Bullosa Simplex Cristina Has, Yow-Ren Chang, Andreas Volz, Doris Hoeping,

Journal of Investigative Dermatology

Presentation transcript:

Genetic Reversion via Mitotic Recombination in Ichthyosis with Confetti due to a KRT10 Polyalanine Frameshift Mutation Young H. Lim, Jingyao Qiu, Corey Saraceni, Barbara A. Burrall, Keith A. Choate Journal of Investigative Dermatology Volume 136, Issue 8, Pages 1725-1728 (August 2016) DOI: 10.1016/j.jid.2016.04.023 Copyright © 2016 The Authors Terms and Conditions

Figure 1 Clinical features and histopathology. (a) Right forearm demonstrating marked erythema, fine white scale, and numerous small white spots, all less than 5 mm in size. Pen markings designate 2 of 3 sites at which biopsies were performed. (b, c, d) ×20 histology of red affected skin, revertant skin, and normal control, respectively, showing the basal layer (B), spinous layer (S), granular layer (G) where applicable, and stratum corneum (SC). The affected epidermis demonstrates acanthosis, perinuclear vacuolization, parakeratosis, and loss of the granular layer. Revertant skin shows normal histology. Scale bar: 150 μm. Journal of Investigative Dermatology 2016 136, 1725-1728DOI: (10.1016/j.jid.2016.04.023) Copyright © 2016 The Authors Terms and Conditions

Figure 2 A novel KRT10 mutation encoding a polyalanine motif causes ichthyosis with confetti (IWC) with white spots resulting from loss of heterozygosity (LOH). (a) Sanger sequencing of KRT10 in IWC100 identified a de novo c.1373Gdel mutation affecting the last base of exon 6. (b) This mutation causes entry into a mutant reading frame that abolishes the endogenous glycine-rich tail domain of keratin 10 (K10) with an alanine-rich motif that extends the carboxyl terminus by 19 additional amino acids. (c) Immunohistochemistry of KRT10 demonstrates nucleolar aggregates only in the affected (middle panel), but not revertant (left panel), skin. A higher power (×63) image is included as inset. Primary keratinocytes cultured from a biopsy also demonstrate nucleolar mislocalization of KRT10 that costain with fibrillarin, a nucleolar marker (right panel and inset). Scale bars = 100 μm. (d) LOH mapping demonstrates heterozygous genotype from 17pter to the proximal portion of the q arm, but converts to homozygosity downstream to the telomere without any change in the logR ratio, indicating copy-neutral LOH. Journal of Investigative Dermatology 2016 136, 1725-1728DOI: (10.1016/j.jid.2016.04.023) Copyright © 2016 The Authors Terms and Conditions