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

Slides:

Advertisements

Similar presentations

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

Advertisements

Genetic Heterogeneity of Pseudoxanthoma Elasticum: The Chinese Signature Profile of ABCC6 and ENPP1 Mutations Liang Jin, Qiujie Jiang, Zhengsheng Wu,

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

Epidermolysis Bullosa Simplex Caused by Distal Truncation of BPAG1-e: An Intermediate Generalized Phenotype with Prurigo Papules Iana Turcan, Anna M.G.

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

Genetic Diseases of Junctions

Novel mutations and polymorphisms in the CFTR gene associated with three subtypes of congenital absence of vas deferens Xiaojian Yang, M.D., Qipeng Sun,

Dystrophic Epidermolysis Bullosa: COL7A1 Mutation Landscape in a Multi-Ethnic Cohort of 152 Extended Families with High Degree of Customary Consanguineous.

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,

Mutational Spectrum of d-Bifunctional Protein Deficiency and Structure-Based Genotype-Phenotype Analysis Sacha Ferdinandusse, Mari S. Ylianttila, Jolein.

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

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

A Novel Keratin 5 Mutation (K5V186L) in a Family with EBS-K: a Conservative Substitution Can Lead to Development of Different Disease Phenotypes Mirjana.

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

Efrat Avigad Laron, Emil Aamar, David Enshell-Seijffers

Whole Genome Linkage Analysis Followed by Whole Exome Sequencing Identifies Nicastrin (NCSTN) as a Causative Gene in a Multiplex Family with γ-Secretase.

Mutations in a Novel Gene with Transmembrane Domains Underlie Usher Syndrome Type 3 Tarja Joensuu, Riikka Hämäläinen, Bo Yuan, Cheryl Johnson, Saara.

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,

Molecular Dynamics Simulation of the Consequences of a PYCR1 Mutation (p.Ala189Val) in Patients with Complex Connective Tissue Disorder and Severe Intellectual.

The Genetic Basis of Pachyonychia Congenita

Volume 117, Issue 3, Pages (September 1999)

Size Polymorphisms in the Human Ultrahigh Sulfur Hair Keratin-Associated Protein 4, KAP4, Gene Family Naoyuki Kariya, Yutaka Shimomura, Masaaki Ito

Peter Ianakiev, Michael W

Elizabeth R. Heller, Sikandar G

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

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

Multigene Next-Generation Sequencing Panel Identifies Pathogenic Variants in Patients with Unknown Subtype of Epidermolysis Bullosa: Subclassification.

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

Mutations in the Lipase H Gene Underlie Autosomal Recessive Woolly Hair/Hypotrichosis Yutaka Shimomura, Muhammad Wajid, Lynn Petukhova, Lawrence Shapiro,

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

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

A Missense Mutation in the Zinc-Finger Domain of the Human Hairless Gene Underlies Congenital Atrichia in a Family of Irish Travellers Wasim Ahmad, Alan.

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

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

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

A Mutation in the Variable Repeat Region of the Aggrecan Gene (AGC1) Causes a Form of Spondyloepiphyseal Dysplasia Associated with Severe, Premature.

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.

Severe Chilblain Lupus Is Associated with Heterozygous Missense Mutations of Catalytic Amino Acids or their Adjacent Mutations in the Exonuclease Domains.

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

Abnormal Cornified Cell Envelope Formation in Mutilating Palmoplantar Keratoderma Unrelated to Epidermal Differentiation Complex Masashi Akiyama, Angela.

KRT5 and KRT14 Mutations in Epidermolysis Bullosa Simplex with Phenotypic Heterogeneity, and Evidence of Semidominant Inheritance in a Multiplex Family

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

The Kindler Syndrome: A Spectrum of FERMT1 Mutations in Iranian Families Leila Youssefian, Hassan Vahidnezhad, Mohammadreza Barzegar, Qiaoli Li, Soheila.

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.

Compound Heterozygosity for Non-Sense and Mis-Sense Mutations in Desmoplakin Underlies Skin Fragility/Woolly Hair Syndrome Neil V. Whittock, Hong Wan,

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

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

Disruption of ERBB2IP Is not Associated with Dystrophic Epidermolysis Bullosa in Both Father and Son Carrying a Balanced 5;13 Translocation Margarita.

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

Binding Affinity and Interaction of LL-37 with HLA-C

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

Bruce L. Zuraw, MD, Jack Herschbach, BA

Hirokatsu Yanagihori, Noritaka Oyama, Koichiro Nakamura, Fumio Kaneko

Recurrent Mutations in Kindlin-1, a Novel Keratinocyte Focal Contact Protein, in the Autosomal Recessive Skin Fragility and Photosensitivity Disorder,

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

Volume 71, Issue 6, Pages (March 2007)

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

The South African “Bathing Suit Ichthyosis” Is a Form of Lamellar Ichthyosis Caused by a Homozygous Missense Mutation, p.R315L, in Transglutaminase 1

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

Ellen Pfendner, Jouni Uitto Journal of Investigative Dermatology

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

Mutational Spectrum of d-Bifunctional Protein Deficiency and Structure-Based Genotype-Phenotype Analysis Sacha Ferdinandusse, Mari S. Ylianttila, Jolein.

Presentation transcript:

Gene-Targeted Next Generation Sequencing Identifies PNPLA1 Mutations in Patients with a Phenotypic Spectrum of Autosomal Recessive Congenital Ichthyosis: The Impact of Consanguinity Hassan Vahidnezhad, Leila Youssefian, Amir Hossein Saeidian, Sirous Zeinali, Parvin Mansouri, Soheila Sotoudeh, Mohammadreza Barzegar, Javad Mohammadi-asl, Razieh Karamzadeh, Maryam Abiri, Kevin McCormick, Paolo Fortina, Jouni Uitto Journal of Investigative Dermatology Volume 137, Issue 3, Pages 678-685 (March 2017) DOI: 10.1016/j.jid.2016.11.012 Copyright © 2016 The Authors Terms and Conditions

Figure 1 Clinical features and histopathology of patients with PNPLA1 mutations. (a–f, k, o) Note hyperkeratotic scaly lesions with ectropion, as well as (h) hyperlinearity of the palms, and (i, j) acrogeric features on the backs of the hands in a 7-year-old patient, and (l) of a 32-year old patient. Also note (d, g) erythroderma, (f, g) malformation of the outer ears, and (m, n) nail dystrophy. (p) Characteristic histopathological findings include lamellar orthokeratosis, focal parakeratosis, and mild psoriasiform acanthosis; granular layer appears normal in epidermis. In the upper dermis, there is vascular proliferation, ectasia, and sparse perivascular inflammatory cell infiltrate. Scale bar = 50 μm). (q–t) Illustration of the evolvement of the clinical phenotype of the 8-year-old patient shown in d and g, showing (q, r) collodion membrane at birth, (s, t) which resolved 1 year later. All subjects and parents of underaged patients gave written informed consent to publish their images. Journal of Investigative Dermatology 2017 137, 678-685DOI: (10.1016/j.jid.2016.11.012) Copyright © 2016 The Authors Terms and Conditions

Figure 2 Family pedigrees and identification of mutations in PNPLA1 in nine families with ichthyosis. (a–i) The probands are indicated by arrowheads, and the affected individuals tested for mutations are identified by a number (family-patient) to allow reference to Supplementary Table S1. The parents of the probands in whom the mutations were verified in the heterozygous state are indicated by red asterisks. Note the consanguinity in all families; the parents of the probands are in most cases first cousins (Table 1). The positions of the homozygous nucleotide substitutions resulting in missense mutations are indicated by red arrows. Journal of Investigative Dermatology 2017 137, 678-685DOI: (10.1016/j.jid.2016.11.012) Copyright © 2016 The Authors Terms and Conditions

Figure 3 Gene and protein structures of PNPLA1 and the positions of pathogenic mutations. (a) The PNPLA1 gene consists of eight exons with their sizes (bp) indicated in parenthesis. (The introns are not drawn to scale). The genomic sequences encoding patatin-like and proline-rich domains are indicated. Amino acid residues essential for enzymatic activity are indicated by yellow triangles. The positions of mutations identified in this study that were, to our knowledge, previously unreported are indicated in red above the gene structure, and those previously reported are in black below. Note that all mutations reside within the gene segment encoding the patatin-like protein domain. (b) Structural representation of patatin-like domain of PNPLA1 (residues Ile16-Thr185) with the catalytic center adjacent to residue Ser53 being shown by dashed circle with yellow overlay. Mutations that are likely to interfere with catalytic activity are colored in pink. Mutations that are located at the protein interface are indicated in green. Oxygen, hydrogen, nitrogen, and carbon atoms are in red, white, blue, and cyan, respectively (stick-and-ball structures). Aa, amino acids; bp, base pairs; Ex, exon; TGA, stop codon; UTR, translated region. Journal of Investigative Dermatology 2017 137, 678-685DOI: (10.1016/j.jid.2016.11.012) Copyright © 2016 The Authors Terms and Conditions