Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome.
Warburg Micro syndrome (WARBM1) is a severe autosomal recessive disorder characterized by developmental abnormalities of the eye and central nervous system and by microgenitalia. We identified homozygous inactivating mutations in RAB3GAP, encoding RAB3 GTPase activating protein, a key regulator of the Rab3 pathway implicated in exocytic release of neurotransmitters and hormones, in 12 families with Micro syndrome. We hypothesize that the underlying pathogenesis of Micro syndrome is a failure of exocytic release of ocular and neurodevelopmental trophic factors.
Aligianis
Irene A
IA
Section of Medical and Molecular Genetics, University of Birmingham, Birmingham, B15 2TT, UK.
Johnson
Colin A
CA
Gissen
Paul
P
Chen
Dongrong
D
Hampshire
Daniel
D
Hoffmann
Katrin
K
Maina
Esther N
EN
Morgan
Neil V
NV
Tee
Louise
L
Morton
Jenny
J
Ainsworth
John R
JR
Horn
Denise
D
Rosser
Elisabeth
E
Cole
Trevor R P
TR
Stolte-Dijkstra
Irene
I
Fieggen
Karen
K
Clayton-Smith
Jill
J
Mégarbané
André
A
Shield
Julian P
JP
Newbury-Ecob
Ruth
R
Dobyns
William B
WB
Graham
John M
JM
Kjaer
Klaus W
KW
Warburg
Mette
M
Bond
Jacqueline
J
Trembath
Richard C
RC
Harris
Laura W
LW
Takai
Yoshimi
Y
Mundlos
Stefan
S
Tannahill
David
D
Woods
C Geoffery
CG
Maher
Eamonn R
ER
D020134:Catalytic Domain; D002490:Central Nervous System / Q000002:abnormalities; D005124:Eye Abnormalities / Q000473:pathology; D005835:Genitalia / Q000002:abnormalities; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D013577:Syndrome; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D020691:rab GTP-Binding Proteins