Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Deficiency for the ubiquitin ligase ube3b in a blepharophimosis-ptosis- intellectual-disability syndrome
American Journal of Human Genetics, Volume 91, No. 6, Year 2012
Notification
URL copied to clipboard!
Description
Ubiquitination plays a crucial role in neurodevelopment as exemplified by Angelman syndrome, which is caused by genetic alterations of the ubiquitin ligase-encoding UBE3A gene. Although the function of UBE3A has been widely studied, little is known about its paralog UBE3B. By using exome and capillary sequencing, we here identify biallelic UBE3B mutations in four patients from three unrelated families presenting an autosomal-recessive blepharophimosis- ptosis-intellectual-disability syndrome characterized by developmental delay, growth retardation with a small head circumference, facial dysmorphisms, and low cholesterol levels. UBE3B encodes an uncharacterized E3 ubiquitin ligase. The identified UBE3B variants include one frameshift and two splice-site mutations as well as a missense substitution affecting the highly conserved HECT domain. Disruption of mouse Ube3b leads to reduced viability and recapitulates key aspects of the human disorder, such as reduced weight and brain size and a downregulation of cholesterol synthesis. We establish that the probable Caenorhabditis elegans ortholog of UBE3B, oxi-1, functions in the ubiquitin/proteasome system in vivo and is especially required under oxidative stress conditions. Our data reveal the pleiotropic effects of UBE3B deficiency and reinforce the physiological importance of ubiquitination in neuronal development and function in mammals. © 2012 The American Society of Human Genetics.
Authors & Co-Authors
Basel-Vanagaite, Lina
Israel, Petah Tiqwa
Rabin Medical Center Israel
Israel, Tel Aviv-yafo
Tel Aviv University
Israel, Petah Tiqwa
Schneider Childrens Medical Center Israel
Dallapiccola, Bruno
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Ramírez-Solís, Ramiro
United Kingdom, London
Wellcome Trust
Segref, Alexandra
Germany, Koln
Universität zu Köln
Thiele, Holger
Germany, Koln
Medizinische Fakultät
Edwards, Andrew
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Arends, Mark Johan
United Kingdom, Cambridge
University of Cambridge
Miró, Xavier
Germany, Bonn
Universität Bonn
White, Jacqueline K.
United Kingdom, London
Wellcome Trust
Désir, Julie
Belgium, Brussels
Hôpital Erasme
Abramowicz, Marc Joel
Belgium, Brussels
Hôpital Erasme
Belgium, Brussels
Université Libre de Bruxelles
Dentici, Maria Lisa
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Lepri, Francesca Romana
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Hofmann, Kay
Germany, Koln
Universität zu Köln
Germany, Bergisch Gladbach
Miltenyi Biotec
Har-Zahav, Adi
Israel, Tel Aviv-yafo
Tel Aviv University
Ryder, Edward J.
United Kingdom, London
Wellcome Trust
Karp, Natasha A.
United Kingdom, London
Wellcome Trust
Estabel, Jeanne
United Kingdom, London
Wellcome Trust
Gerdin, Anna Karin B.
United Kingdom, London
Wellcome Trust
Podrini, Christine
United Kingdom, London
Wellcome Trust
Ingham, Neil J.
United Kingdom, London
Wellcome Trust
Altmüller, Janine
Germany, Koln
Medizinische Fakultät
Nürnberg, Gudrun
Germany, Koln
Medizinische Fakultät
Frommolt, Peter
Germany, Koln
Universität zu Köln
Germany, Koln
Medizinische Fakultät
Abdelhak, Sonia
Tunisia, Tunis
Institut Pasteur de Tunis
Pasmanik-Chor, Metsada
Israel, Tel Aviv-yafo
Tel Aviv University
Konen, Osnat
Israel, Tel Aviv-yafo
Tel Aviv University
Israel, Petah Tiqwa
Schneider Childrens Medical Center Israel
Kelley, Richard I.
United States, Baltimore
Kennedy Krieger Institute
Shohat, Mordechai
Israel, Petah Tiqwa
Rabin Medical Center Israel
Israel, Tel Aviv-yafo
Tel Aviv University
Nürnberg, Peter
Germany, Koln
Universität zu Köln
Germany, Koln
Medizinische Fakultät
Flint, Jonathan
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Steel, Karen P.
United Kingdom, London
Wellcome Trust
Hoppe, Thorsten
Germany, Koln
Universität zu Köln
Kubisch, Christian
Germany, Ulm
Universität Ulm
Adams, David James
United Kingdom, London
Wellcome Trust
Borck, Guntram
Germany, Ulm
Universität Ulm
Statistics
Citations: 36
Authors: 36
Affiliations: 16
Identifiers
Doi:
10.1016/j.ajhg.2012.10.011
ISSN:
00029297
e-ISSN:
15376605
Research Areas
Disability
Genetics And Genomics