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

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

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

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

Herlitz Junctional Epidermolysis Bullosa: Novel and Recurrent Mutations in the LAMB3 Gene and the Population Carrier Frequency Aoi Nakano, Ellen Pfendner,

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

Abraham Zlotogorski Journal of Investigative Dermatology

Olmsted Syndrome Caused by a Homozygous Recessive Mutation in TRPV3

Combination of a Novel Frameshift Mutation (1929delCA) and a Recurrent Nonsense Mutation (W610X) of the LAMB3 Gene in a Japanese Patient with Herlitz.

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

A Missense Mutation in CDH3, Encoding P-Cadherin, Causes Hypotrichosis with Juvenile Macular Dystrophy Margarita Indelman, Reuven Bergman, Danny Petronius,

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

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

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

Olmsted Syndrome Caused by a Homozygous Recessive Mutation in TRPV3

A Novel Mutation in the L12 Domain of Keratin 5 in the Köbner Variant of Epidermolysis Bullosa Simplex Philippa Galligan, Pawel Listwan, Gregory M. Siller,

Progress in Molecular Genetics of Heritable Skin Diseases: The Paradigms of Epidermolysis Bullosa and Pseudoxanthoma Elasticum Jouni Uitto, Leena Pulkkinen,

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

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

A Recurrent Intragenic Deletion in the Desmoglein 4 Gene Underlies Localized Autosomal Recessive Hypotrichosis Celia Moss, Amalia Martinez-Mir, HaMut.

Peter Ianakiev, Michael W

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

Novel SLC39A4 Mutations in Acrodermatitis Enteropathica

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

Identification of a Novel Mutation R42P in the Gap Junction Protein β-3 Associated with Autosomal Dominant Erythrokeratoderma Variabilis Amanda Wilgoss,

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

Margarita Indelman, Reuven Bergman, Michal Ramon, Eli Sprecher

Qiaoli Li, Dorothy K. Grange, Nicole L. Armstrong, Alison J

Laminin-5 Mutational Analysis in an Italian Cohort of Patients with Junctional Epidermolysis Bullosa Patrizia Posteraro, Naomi De Luca, Guerrino Meneguzzi,

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,

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

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.

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

Long-Range Polymerase Chain Reaction for Specific Full-Length Amplification of the Human Keratin 14 Gene and Novel Keratin 14 Mutations in Epidermolysis.

Eli Sprecher, Christopher J. Miller, Gabriele Richard

Allelic Heterogeneity of Dominant and Recessive COL7A1 Mutations Underlying Epidermolysis Bullosa Pruriginosa Jemima E. Mellerio, Gabrielle H.S. Ashton,

Maternal Uniparental Meroisodisomy in the LAMB3 Region of Chromosome 1 Results in Lethal Junctional Epidermolysis Bullosa Yasuko Takizawa, Leena Pulkkinen,

A Recurrent Mutation in the ARS (Component B) Gene Encoding SLURP-1 in Turkish Families with Mal de Meleda: Evidence of a Founder Effect Guofang Hu,

Deletion of the Cytoplasmatic Domain of BP180/Collagen XVII Causes a Phenotype with Predominant Features of Epidermolysis Bullosa Simplex Marcel Huber,

A Novel Point Mutation Affecting the Tyrosine Kinase Domain of the TRKA Gene in a Family with Congenital Insensitivity to Pain with Anhidrosis Shinichi.

Neil V. Whittock, Gabrielle H. S. Ashton, Patricia J. C

Expanding The Phenotypic Spectrum of Cx26 Disorders: Bart–Pumphrey Syndrome is Caused by a Novel Missense Mutation in GJB2 Gabriele Richard, Nkecha Brown,

Homozygous Dominant Missense Mutation in Keratin 17 Leads to Alopecia in Addition to Severe Pachyonychia Congenita Neil J. Wilson, Mónica L. Cárdenas.

A Novel Arginine→Serine Mutation in EDA1 in a Japanese Family with X-Linked Anhidrotic Ectodermal Dysplasia Noriaki Aoki, Kaoru Ito, Toshiaki Tachibana,

A Novel Recessive Connexin 31 (GJB3) Mutation in a Case of Erythrokeratodermia Variabilis Alessandro Terrinoni, Aida Leta, Cristina Pedicelli, Eleonora.

Opitz G/BBB Syndrome in Xp22: Mutations in the MID1 Gene Cluster in the Carboxy- Terminal Domain Karin Gaudenz, Erich Roessler, Nandita Quaderi, Brunella.

Maternal Transmission of the 3 bp Deletion within Exon 7 of the STS Gene in Steroid Sulfatase Deficiency Margarita Valdes-Flores Journal of Investigative.

Homozygous Variegate Porphyria: Identification of Mutations on Both Alleles of the Protoporphyrinogen Oxidase Gene in a Severely Affected Proband Jorge.

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

Molecular Heterogeneity of Epidermolysis Bullosa Simplex: Contribution of EXPH5 Mutations Manuela Pigors, Agnes Schwieger-Briel, Juna Leppert, Dimitra.

Identification of a Lethal Form of Epidermolysis Bullosa Simplex Associated with a Homozygous Genetic Mutation in Plectin Maryse Bonduelle, Linda De.

Normophosphatemic Familial Tumoral Calcinosis Is Caused by Deleterious Mutations in SAMD9, Encoding a TNF-α Responsive Protein Ilana Chefetz, Danny Ben.

Identification of Recurrent Mutations in the ARS (Component B) Gene Encoding SLURP-1 in Two Families with Mal de Meleda Kimberley Morine Ward, Jülide.

The 97 kDa Linear IgA Bullous Dermatosis Antigen is not Expressed in a Patient with Generalized Atrophic Benign Epidermolysis Bullosa with a Novel Homozygous.

A Deleterious Mutation in SAMD9 Causes Normophosphatemic Familial Tumoral Calcinosis Orit Topaz, Margarita Indelman, Ilana Chefetz, Dan Geiger, Aryeh.

Early Death from Cardiomyopathy in a Family with Autosomal Dominant Striate Palmoplantar Keratoderma and Woolly Hair Associated with a Novel Insertion.

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

Anthony M. Raizis, Martin M. Ferguson, David T. Nicholls, Derek W

Ellen Pfendner, Jouni Uitto 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,

Epidermolysis Bullosa: The Expanding Mutation Database

Is Screening of the Candidate Gene Necessary in Unrelated Partners of Members of Families with Herlitz Junctional Epidermolysis Bullosa? Alfred Klausegger,

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

A Mutation in LIPN, Encoding Epidermal Lipase N, Causes a Late-Onset Form of Autosomal-Recessive Congenital Ichthyosis Shirli Israeli, Ziyad Khamaysi,

Novel Mutations in the LAMB3 Gene Shared by Two Japanese Unrelated Families with Herlitz Junctional Epidermolysis Bullosa, and Their Application for Prenatal.

Identification of Novel pro-α2(IX) Collagen Gene Mutations in Two Families with Distinctive Oligo-Epiphyseal Forms of Multiple Epiphyseal Dysplasia Paul.

Presentation transcript:

Epidermolytic Hyperkeratosis and Epidermolysis Bullosa Simplex Caused by Frameshift Mutations Altering the V2 Tail Domains of Keratin 1 and Keratin 5 Eli Sprecher, Gil Yosipovitch, Reuven Bergman, Dan Ciubutaro, Margarita Indelman, Ellen Pfendner, Leok C. Goh, Christopher J. Miller, Jouni Uitto, Gabriele Richard Journal of Investigative Dermatology Volume 120, Issue 4, Pages 623-626 (April 2003) DOI: 10.1046/j.1523-1747.2003.12084.x Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 A mutation affecting the K1 tail causes atypical EHK. (a) Pedigree of the affected family. The filled symbol indicates the affected individual. (b) Thickened hyperkeratotic plaques with underlying erythema and fissuring on the palms of both hands. (c) Well-demarcated hyperkeratotic plaques with a cobblestone surface pattern over the right knee. Note several islands of superficial peeling (arrows). (d) Diffuse plantar keratoderma with prominent fissuring. (e) Thick, well-demarcated hyperkeratotic plaques with fine scales over the elbows. (f) Histopathologic examination reveals orthokeratotic hyperkeratosis, hypergranulosis, church-spire-like papillomatosis, and areas suggestive of vacuolar degeneration (arrows) (hematoxylin-eosin, 400×). A few binucleated cells are present in the granular layer (insert; 630×). (g) Mutation analysis of the proband reveals a G insertion at nucleotide position 1752 (arrow) in exon 9 of K1 (central panel) compared to the wild-type sequence in the mother (right panel) and father (left panel) of the proband. Sequence chromatograms depict the antisense strand because of the presence of a heterozygous 21bp deletion polymorphism (Korge et al, 1992) upstream of the mutation. (h) Comparison of the amino acid sequence of wild-type (black) and mutant (red) K1 spanning the V2 domain. Numbers denote the amino acid positions. The recurrent glycine loop motifs (Korge et al, 1992) are shown in boxes. Journal of Investigative Dermatology 2003 120, 623-626DOI: (10.1046/j.1523-1747.2003.12084.x) Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 A mutation affecting the K5 tail causes EBS. (a) Pedigree of the affected family. The filled symbol indicates the affected individual. Mutation 1635delG abolishes a recognition site for the endonuclease BanII. PCR fragments amplified from exon 9 were digested with BanII. A novel 268bp fragment is observed in the affected patient only. (b) Mutation analysis. The proband was found to carry a heterozygous G deletion at position 1635 of KRT5 (upper panel). The wild-type sequence is shown for comparison (lower panel). (c) Comparison of the amino acid sequence of wild-type (black) and mutant (red) K5 spanning part of the V2 domain. Numbers denote amino acid positions. The 1635delG mutation leads to the generation of an aberrant and elongated K5 tail domain. Journal of Investigative Dermatology 2003 120, 623-626DOI: (10.1046/j.1523-1747.2003.12084.x) Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions