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  • Mutations in the small GTPase gene RAB39B are responsible for X-linked mental retardation associated with autism, epilepsy, and macrocephaly
    Giannandrea, Maila ...
    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 intracellularvesicular trafficking, have been shown to be involved in MR. We report here the identification of mutations in the small GTPase RAB39B gene intwo 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 withthe 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 unknownfunction, is a neuronal-specific protein that is localized to the Golgicompartment. Its downregulation leads to an alteration in the number andmorphology 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 neuronalalteration as a consequence of downregulation of RAB39B and emphasize the critical role of vesicular trafficking in the development of neurons and human intellectual abilities.
    Vir: American journal of human genetics. - ISSN 0002-9297 (Vol. 86, issue 2, 2010, str. 185-195)
    Vrsta gradiva - članek, sestavni del
    Leto - 2010
    Jezik - angleški
    COBISS.SI-ID - 29038297
    DOI

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