GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:20159109

From GONUTS
Jump to: navigation, search
Citation

Giannandrea, M, Bianchi, V, Mignogna, ML, Sirri, A, Carrabino, S, D'Elia, E, Vecellio, M, Russo, S, Cogliati, F, Larizza, L, Ropers, HH, Tzschach, A, Kalscheuer, V, Oehl-Jaschkowitz, B, Skinner, C, Schwartz, CE, Gecz, J, Van Esch, H, Raynaud, M, Chelly, J, de Brouwer, AP, Toniolo, D and D'Adamo, P (2010) Mutations in the small GTPase gene RAB39B are responsible for X-linked mental retardation associated with autism, epilepsy, and macrocephaly. Am. J. Hum. Genet. 86:185-95

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.

Links

PubMed PMC2820185 Online version:10.1016/j.ajhg.2010.01.011

Keywords

Animals; Autistic Disorder/complications; Autistic Disorder/genetics; Base Sequence; Brain/metabolism; Brain/pathology; Cell Differentiation; Craniofacial Abnormalities/complications; Craniofacial Abnormalities/genetics; DNA Mutational Analysis; Down-Regulation/genetics; Epilepsy/complications; Epilepsy/genetics; Female; Golgi Apparatus/metabolism; HeLa Cells; Humans; Male; Mental Retardation, X-Linked/complications; Mental Retardation, X-Linked/genetics; Mice; Molecular Sequence Data; Mutation/genetics; Neurons/metabolism; Neurons/pathology; Organ Specificity/genetics; Pedigree; Protein Transport; RNA, Small Interfering/metabolism; Synapses/genetics; rab GTP-Binding Proteins/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:RB39B

involved_in

GO:0016192: vesicle-mediated transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:RB39B

located_in

GO:0005794: Golgi apparatus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:RB39B

involved_in

GO:0050808: synapse organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RB39B

located_in

GO:0005794: Golgi apparatus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.