Presentation is loading. Please wait.

Presentation is loading. Please wait.

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.

Published byDina Park Modified over 5 years ago

Similar presentations

Presentation on theme: "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."— Presentation transcript:

1 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 Hogan, Patricia J.C. Dopping-Hepenstal, Beatriz C. Winik, Raúl A. Asial, Richard Dobson, Charles A. Mein, Patricia A. Baselaga, Jemima E. Mellerio, Arti Nanda, Maria del Carmen Boente, David P. Kelsell, John A. McGrath, Andrew P. South  Journal of Investigative Dermatology  Volume 130, Issue 6, Pages (June 2010) DOI: /jid Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions

2 Figure 1 Clinical features and immunohistochemistry. (a) Clinical features showing distinct phenotype of skin fragility, woolly hair, and palmoplantar keratoderma in affected patients from Argentina (top panel) and Kuwait (middle and lower panels). (b) Immunohistochemistry with monoclonal C- (PG5.1) and N-terminal (15F11) PG antibodies shows barely detectable PG in skin sections from patients A and K. (c) Immunohistochemistry shows normal adherens junction protein distribution in skin sections from control, parent A, and patient A (p.S24X). Scale bar=50μm. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions

3 Figure 2 Two previously unreported homozygous mutations locate within the 5′ end of the JUP gene. (a) Electropherograms showing wild-type control and mutant nucleotide sequences in the second and third exons of JUP. Sequencing of patient A's DNA (upper right panel) reveals a homozygous transversion from cytosine to adenine at position 71, which changes a serine amino-acid codon, TCG, to a stop codon, TAG (c.71C>A, p.S24X). Sequencing of patient K's DNA (lower right panel) reveals a homozygous transition from guanine to adenine at position 468, which is predicted to abolish the natural splice donor of exon 3 (c.468G>A). Unaffected parents are heterozygous carriers of these mutations. (b) Automated splice site analyses predict the abolition of the natural splice donor of exon 3 after transition from guanine to adenine at position 468. (c) Schematic diagram of JUP exons 1–3 showing the site of the c.468G>A and p.S24X mutations. The native Kozak consensus sequence of JUP and three possible alternative translation start sites downstream of the p.S24X mutation are shown. The very next ATG at methionine 43 (M43) has the strongest Kozak sequence represented by an adenine at conserved position -3 and a guanine at conserved position +4, as observed for the native Kozak sequence (M1). (d) Schematic diagram showing the positions of p.S24X and c.468G>A mutations (boxed), as well as the two previously characterized mutations relative to the O-glycosylation site, the putative destruction box, and the armadillo repeats of the PG protein. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions

4 Figure 3 p.S24X mutation results in detectable mutant transcript and reduced levels of truncated protein in the skin. (a) Sequencing analysis of RT–PCR products generated with primers spanning exons 1–3 shows the presence of a mutant transcript in both parental and patient A samples, indicating that normal 5′ splicing is occurring. (b) Western blotting of skin proteins isolated from normal control (c), maternal (M), and patient (P) samples using a C-terminal PG antibody (PG5.1) shows low levels of a truncated protein in both maternal and patient samples. β-Actin was used as a loading control. (c) PGΔN42 is efficiently translated in human dermal fibroblasts. pBabe puro constructs containing vector alone (Vector), wild-type PG (WT), or p.S24X PG (S24X) were expressed in dermal fibroblasts, and PG reactive protein was detected by western blotting and an anti-PG antibody, PG5.1. NHK, normal human keratinocyte control. (d) Densitometry was used to calculate the amount of recombinant S24X protein in C (left) relative to wild type. Quantitative RT-PCR of cells expressing pBabe vectors from C reveals an increased level of p.S24X mRNA in dermal fibroblasts expressing S24X mutant PG compared with wild-type PG (right). This increase is reflected by the increased amount of protein shown: 4.2-fold more mRNA vs 5.2-fold more protein, respectively, indicating that the amount of PGΔN42 protein reflects the amount of mRNA relative to wild-type PG and that efficient translation takes place. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions

Download ppt "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."

Similar presentations

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

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 

Epidermolysis Bullosa: Novel and De Novo Premature Termination Codon and Deletion Mutations in the Plectin Gene Predict Late-Onset Muscular Dystrophy 
Identification of EpCAM as the Gene for Congenital Tufting Enteropathy

Identification of EpCAM as the Gene for Congenital Tufting Enteropathy
A PLEC Isoform Identified in Skin, Muscle, and Heart

A PLEC Isoform Identified in Skin, Muscle, and Heart
Genetic Heterogeneity of Pseudoxanthoma Elasticum: The Chinese Signature Profile of ABCC6 and ENPP1 Mutations  Liang Jin, Qiujie Jiang, Zhengsheng Wu,

Genetic Heterogeneity of Pseudoxanthoma Elasticum: The Chinese Signature Profile of ABCC6 and ENPP1 Mutations  Liang Jin, Qiujie Jiang, Zhengsheng Wu,
Crucial Roles of MZF1 and Sp1 in the Transcriptional Regulation of the Peptidylarginine Deiminase Type I Gene (PADI1) in Human Keratinocytes  Sijun Dong,

Crucial Roles of MZF1 and Sp1 in the Transcriptional Regulation of the Peptidylarginine Deiminase Type I Gene (PADI1) in Human Keratinocytes  Sijun Dong,
A Novel Mutation and Large Size Polymorphism Affecting the V2 Domain of Keratin 1 in an African-American Family with Severe, Diffuse Palmoplantar Keratoderma.

A Novel Mutation and Large Size Polymorphism Affecting the V2 Domain of Keratin 1 in an African-American Family with Severe, Diffuse Palmoplantar Keratoderma.
Eija Siintola, Meral Topcu, Nina Aula, Hannes Lohi, Berge A

Eija Siintola, Meral Topcu, Nina Aula, Hannes Lohi, Berge A
Zebrafish as a Model System to Study Skin Biology and Pathology

Zebrafish as a Model System to Study Skin Biology and Pathology
Mutations in the Keratin 85 (KRT85/hHb5) Gene Underlie Pure Hair and Nail Ectodermal Dysplasia  Yutaka Shimomura, Muhammad Wajid, Mazen Kurban, Nobuyuki.

Mutations in the Keratin 85 (KRT85/hHb5) Gene Underlie Pure Hair and Nail Ectodermal Dysplasia  Yutaka Shimomura, Muhammad Wajid, Mazen Kurban, Nobuyuki.
IFN-γ Upregulates Expression of the Mouse Complement C1rA Gene in Keratinocytes via IFN-Regulatory Factor-1  Sung June Byun, Ik-Soo Jeon, Hyangkyu Lee,

IFN-γ Upregulates Expression of the Mouse Complement C1rA Gene in Keratinocytes via IFN-Regulatory Factor-1  Sung June Byun, Ik-Soo Jeon, Hyangkyu Lee,
A PLEC Isoform Identified in Skin, Muscle, and Heart

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

Genomic Amplification of the Human Plakophilin 1 Gene and Detection of a New Mutation in Ectodermal Dysplasia/Skin Fragility Syndrome  Neil V. Whittock,
Rose-Anne Romano, Barbara Birkaya, Satrajit Sinha 

Rose-Anne Romano, Barbara Birkaya, Satrajit Sinha 
Inhibition of DNA Methylation in the COL1A2 Promoter by Anacardic Acid Prevents UV- Induced Decrease of Type I Procollagen Expression  Min-Kyoung Kim,

Inhibition of DNA Methylation in the COL1A2 Promoter by Anacardic Acid Prevents UV- Induced Decrease of Type I Procollagen Expression  Min-Kyoung Kim,
Aoi Nakano, Hajime Nakano, Sal LaForgia, Leena Pulkkinen, Jouni Uitto 

Aoi Nakano, Hajime Nakano, Sal LaForgia, Leena Pulkkinen, Jouni Uitto 
Mutations of the SYCP3 Gene in Women with Recurrent Pregnancy Loss

Mutations of the SYCP3 Gene in Women with Recurrent Pregnancy Loss
Single Amino Acid Deletion in Kindlin-1 Results in Partial Protein Degradation Which Can Be Rescued by Chaperone Treatment  Kristin Maier, Yinghong He,

Single Amino Acid Deletion in Kindlin-1 Results in Partial Protein Degradation Which Can Be Rescued by Chaperone Treatment  Kristin Maier, Yinghong He,
Colocalization of Kindlin-1, Kindlin-2, and Migfilin at Keratinocyte Focal Adhesion and Relevance to the Pathophysiology of Kindler Syndrome  J.E. Lai-Cheong,

Colocalization of Kindlin-1, Kindlin-2, and Migfilin at Keratinocyte Focal Adhesion and Relevance to the Pathophysiology of Kindler Syndrome  J.E. Lai-Cheong,
Mutations in a Novel Gene with Transmembrane Domains Underlie Usher Syndrome Type 3  Tarja Joensuu, Riikka Hämäläinen, Bo Yuan, Cheryl Johnson, Saara.

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

Similar presentations

Ads by Google