scholarly journals Angioid Streaks in Pseudoxanthoma Elasticum: Role of the p.R1268Q Mutation in the ABCC6 Gene

2011 ◽  
Vol 131 (3) ◽  
pp. 782-785 ◽  
Author(s):  
Qiaoli Li ◽  
Sara Sadowski ◽  
Jouni Uitto
Keyword(s):  
Pseudoxanthoma Elasticum ◽  
Angioid Streaks ◽  
Abcc6 Gene

scholarly journals ABCC6 Gene Analysis in 20 Japanese Patients with Angioid Streaks Revealing Four Frequent and Two Novel Variants and Pseudodominant Inheritance

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Satoshi Katagiri ◽  
Yuya Negishi ◽  
Kei Mizobuchi ◽  
Mitsuyoshi Urashima ◽  
Tadashi Nakano ◽  
...  
Keyword(s):  
Medical Records ◽  
Sanger Sequencing ◽  
Pseudoxanthoma Elasticum ◽  
Japanese Patients ◽  
Compound Heterozygous ◽  
Angioid Streaks ◽  
Dermatological Examination ◽  
Abcc6 Gene ◽  
Novel Variants ◽  
Unknown Significance

Purpose. To report the spectrum of ABCC6 variants in Japanese patients with angioid streaks (AS). Patients and Methods. This was a single-center cohort study. The medical records of 20 patients with AS from 18 unrelated Japanese families were retrospectively reviewed. Screening of the ABCC6 gene (exons 1 to 31) was performed using PCR-based Sanger sequencing. Results. Eight ABCC6 variants were identified as candidate disease-causing variants. These eight variants included five known variants (p.Q378X, p.R419Q, p.V848CfsX83, p.R1114C, and p.R1357W), one previously reported variant (p.N428S) of unknown significance, and two novel variants (c.1939C>T [p.H647Y] and c.3374C>T [p.S1125F]); the three latter variants were determined to be variants of significance. The following four variants were frequently identified: p.V848CfsX83 (14/40 alleles, 35.0%), p.Q378X (7/40 alleles, 17.5%), p.R1357W (6/40 alleles, 15.0%), and p.R419Q (4/40 alleles, 10.0%). The ABCC6 variants were identified in compound heterozygous or homozygous states in 13 of 18 probands. Two families showed a pseudodominant inheritance pattern. Pseudoxanthoma elasticum was seen in 15 of 17 patients (88.2%) who underwent dermatological examination. Conclusions. We identified disease-causing ABCC6 variants that were in homozygous or compound heterozygous states in 13 of 18 families (72.2%). Our results indicated that ABCC6 variants play a significant role in patients with AS in the Japanese population.

scholarly journals Role of Serum Fetuin-A, a Major Inhibitor of Systemic Calcification, in Pseudoxanthoma Elasticum

2006 ◽  
Vol 52 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Doris Hendig ◽  
Veronika Schulz ◽  
Marius Arndt ◽  
Christiane Szliska ◽  
Knut Kleesiek ◽  
...  
Keyword(s):  
Blood Donors ◽  
Family Members ◽  
Gene Mutations ◽  
Pseudoxanthoma Elasticum ◽  
Elastic Fibers ◽  
Fetuin A ◽  
Cardiovascular Involvement ◽  
Abcc6 Gene ◽  
Sandwich Enzyme Immunoassay

Abstract Background: Pseudoxanthoma elasticum (PXE) is a hereditary disorder of the connective tissue affecting the skin, retina, and cardiovascular system and characterized by progressive calcification of abnormal and fragmented elastic fibers in the extracellular matrix. The aim of the present study was to investigate the association of fetuin-A, a major systemic inhibitor of calcification, with PXE. Methods: Fetuin-A was measured by quantitative sandwich enzyme immunoassay in sera from 110 German patients with PXE, 53 unaffected first-degree family members, and 80 healthy blood donors. We determined the distribution of the fetuin-A polymorphisms c.742C>T (p.T248M) and c.766C>G (p.T256S) in these same 3 groups. The occurrences of the frequent ABCC6 gene mutations c.3421C>T (p.R1141X) and c.EX23_EX29del were also assessed. Results: Serum fetuin-A concentrations in male and female PXE patients were lower than in unaffected first-degree relatives and controls [mean (SD) concentrations, 0.55 (0.11) g/L in patients; 0.70 (0.23) g/L in relatives; and 0.80 (0.23) g/L in controls (P <0.0001)]. Serum fetuin-A was higher in female PXE patients with cardiovascular involvement than in the corresponding male group (P <0.05). The fetuin-A polymorphism frequencies did not differ among PXE patients, family members, and blood donors. Conclusion: A deficiency of multidrug resistance-associated protein 6 leads to alteration of circulating substrates, e.g., inhibitors of calcification as fetuin-A, leading to progressive mineralization of elastic fibers in PXE.

scholarly journals Dysregulation of gene expression in ABCC6 knockdown HepG2 cells

2014 ◽  
Vol 19 (4) ◽  
Author(s):  
Rocchina Miglionico ◽  
Maria Armentano ◽  
Monica Carmosino ◽  
Antonella Salvia ◽  
Flavia Cuviello ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Autosomal Recessive ◽  
Pseudoxanthoma Elasticum ◽  
Arterial Calcification ◽  
Elastic Fibers ◽  
Ectopic Calcification ◽  
Ectopic Mineralization ◽  
Abcc6 Gene ◽  
Basolateral Plasma Membrane

AbstractABCC6 protein is an ATP-dependent transporter that is mainly found in the basolateral plasma membrane of hepatocytes. ABCC6 deficiency is the primary cause of several forms of ectopic mineralization syndrome. Mutations in the human ABCC6 gene cause pseudoxanthoma elasticum (PXE), an autosomal recessive disease characterized by ectopic calcification of the elastic fibers in dermal, ocular and vascular tissues. Mutations in the mouse ABCC6 gene were also associated with dystrophic cardiac calcification. Reduced levels of ABCC6 protein were found in a β-thalassemic mouse model. Moreover, some cases of generalized arterial calcification in infancy are due to ABCC6 mutations. In order to study the role of ABCC6 in the pathogenesis of ectopic mineralization, the expressions of genes involved in this process were evaluated in HepG2 cells upon stable knockdown of ABCC6 by small hairpin RNA (shRNA) technology. ABCC6 knockdown in HepG2 cells causes a significant upregulation of the genes promoting mineralization, such as TNAP, and a parallel downregulation of genes with anti-mineralization activity, such as NT5E, Fetuin A and Osteopontin. Although the absence of ABCC6 has been already associated with ectopic mineralization syndromes, this study is the first to show a direct relationship between reduced ABCC6 levels and the expression of pro-mineralization genes in hepatocytes.

Novel mutations of ABCC6 gene in Japanese patients with Angioid streaks

2009 ◽  
Vol 380 (3) ◽  
pp. 548-553 ◽  
Author(s):  
Naoyuki Sato ◽  
Tomohiro Nakayama ◽  
Yoshihiro Mizutani ◽  
Mitsuko Yuzawa
Keyword(s):  
Japanese Patients ◽  
Angioid Streaks ◽  
Novel Mutations ◽  
Abcc6 Gene

Disk Drusen and Angioid Streaks in Pseudoxanthoma Elasticum

1991 ◽  
Vol 112 (2) ◽  
pp. 166-170 ◽  
Author(s):  
Kate Coleman ◽  
Monique Hope Ross ◽  
Mary Mc Cabe ◽  
Rosemary Coleman ◽  
David Mooney
Keyword(s):  
Pseudoxanthoma Elasticum ◽  
Angioid Streaks

Angioid streaks beyond pseudoxanthoma elasticum

2010 ◽  
Vol 88 ◽  
pp. 0-0
Author(s):  
J DE ZAEYTIJD ◽  
OM VANAKKER ◽  
PJ COUCKE ◽  
A DE PAEPE ◽  
BP LEROY
Keyword(s):  
Pseudoxanthoma Elasticum ◽  
Angioid Streaks

MULTIMODAL IMAGING OF FOCAL CHOROIDAL EXCAVATION COMPLICATED BY CHOROIDAL NEOVASCULARIZATION IN A PATIENT WITH ANGIOID STREAKS AND PSEUDOXANTHOMA ELASTICUM

2018 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Bruno Fortaleza de Aquino Ferreira ◽  
Rony Carlos Preti ◽  
Marina Brandão Schmidt ◽  
Leandro Cabral Zacharias ◽  
Walter Yukihiko Takahashi ◽  
...  
Keyword(s):  
Choroidal Neovascularization ◽  
Multimodal Imaging ◽  
Pseudoxanthoma Elasticum ◽  
Angioid Streaks ◽  
Focal Choroidal Excavation
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