Mutations in GDI1 are responsible for X-linked non-specific mental retardation.
Rab GDP-dissociation inhibitors (GDI) are evolutionarily conserved proteins that play an essential role in the recycling of Rab GTPases required for vesicular transport through the secretory pathway. We have found mutations in the GDI1 gene (which encodes uGDI) in two families affected with X-linked non-specific mental retardation. One of the mutations caused a non-conservative substitution (L92P) which reduced binding and recycling of RAB3A, the second was a null mutation. Our results show that both functional and developmental alterations in the neuron may account for the severe impairment of learning abilities as a consequence of mutations in GDI1, emphasizing its critical role in development of human intellectual and learning abilities.
D'Adamo
P
P
Institute of Genetics Biochemistry and Evolution, CNR, Pavia, Italy.
Menegon
A
A
Lo Nigro
C
C
Grasso
M
M
Gulisano
M
M
Tamanini
F
F
Bienvenu
T
T
Gedeon
A K
AK
Oostra
B
B
Wu
S K
SK
Tandon
A
A
Valtorta
F
F
Balch
W E
WE
Chelly
J
J
Toniolo
D
D
D001921:Brain / Q000196:embryology; D018360:Crystallography, X-Ray; D005314:Embryonic and Fetal Development / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008040:Genetic Linkage; D020730:Guanine Nucleotide Dissociation Inhibitors; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D014960:X Chromosome; D020692:rab3 GTP-Binding Proteins
C086796:GDP dissociation inhibitor 1; D020730:Guanine Nucleotide Dissociation Inhibitors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins