English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Mutations in the small GTPase gene RAB39B are responsible for X-linked mental retardation associated with autism, epilepsy, and macrocephaly.

Giannandrea, M., Bianchi, V., Mignogna, M. L., Sirri, A., Carrabino, S., D'Elia, E., et al. (2010). Mutations in the small GTPase gene RAB39B are responsible for X-linked mental retardation associated with autism, epilepsy, and macrocephaly. The American Journal of Human Genetics, 86(2), 185-195. doi:10.1016/j.ajhg.2010.01.011.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7BE4-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7BE5-5
Genre: Journal Article
Alternative Title : Am J Hum Genet

Files

show Files
hide Files
:
main.pdf (Any fulltext), 2MB
 
File Permalink:
-
Name:
main.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute for Molecular Genetics, MBMG; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
eDoc_access: MPG
License:
-

Locators

show

Creators

show
hide
 Creators:
Giannandrea, Maila, Author
Bianchi, Veronica, Author
Mignogna, Maria Lidia, Author
Sirri, Alessandra, Author
Carrabino, Salvatore, Author
D'Elia, Errico, Author
Vecellio, Matteo, Author
Russo, Silvia, Author
Cogliati, Francesca, Author
Larizza, Lidia, Author
Ropers, Hans-Hilger1, Author              
Tzschach, Andreas1, Author              
Kalscheuer, Vera M.2, Author              
Oehl-Jaschkowitz, Barbara, Author
Schwartz, Charles E., Author
Gecz, Jozef, Author
Van Esch, Hilde, Author
Raynaud, Martine, Author
Chelly, Jamel, Author
de Brouwer, Arjan P.M., Author
Toniolo, Daniela, AuthorD'Adamo, Patrizia, Author more..
Affiliations:
1Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              
2Chromosome Rearrangements and Disease (Vera Kalscheuer), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479642              

Content

show
hide
Free keywords: -
 Abstract: Human Mental Retardation (MR) is a common and highly heterogeneous pediatric disorder affecting around 3% of the general population; at least 215 X-linked MR (XLMR) conditions have been described, and mutations have been identified in 83 different genes, encoding proteins with a variety of function, such as chromatin remodeling, synaptic function, and intracellular trafficking. The small GTPases of the RAB family, which play an essential role in intracellular vesicular trafficking, have been shown to be involved in MR. We report here the identification of mutations in the small GTPase RAB39B gene in two male patients. One mutation in family X (D-23) introduced a stop codon seven amino acids after the start codon (c.21C > A; p.Y7X). A second mutation, in the MRX72 family, altered the 5′ splice site (c.215+1G > A) and normal splicing. Neither instance produced a protein. Mutations segregate with the disease in the families, and in some family members intellectual disabilities were associated with autism spectrum disorder, epileptic seizures, and macrocephaly. We show that RAB39B, a novel RAB GTPase of unknown function, is a neuronal-specific protein that is localized to the Golgi compartment. Its downregulation leads to an alteration in the number and morphology of neurite growth cones and a significant reduction in presynaptic buttons, suggesting that RAB39B is required for synapse formation and maintenance. Our results demonstrate developmental and functional neuronal alteration as a consequence of downregulation of RAB39B and emphasize the critical role of vesicular trafficking in the development of neurons and human intellectual abilities.

Details

show
hide
Language(s): eng - English
 Dates: 2010-02-12
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: The American Journal of Human Genetics
  Alternative Title : Am J Hum Genet
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 86 (2) Sequence Number: - Start / End Page: 185 - 195 Identifier: ISSN: 0002-9297