Homozygosity for aquaporin 7 G264V in three unrelated children with hyperglyceroluria and a mild platelet secretion defect.
OBJECTIVE
Aquaporin 7 (AQP7) belongs to the aquaglyceroporin family, which transports glycerol and water. AQP7-deficient mice develop obesity, insulin resistance, and hyperglyceroluria. However, AQP7's pathophysiologic role in humans is not yet known.


METHODS
Three children with psychomotor retardation and hyperglyceroluria were screened for AQP7 mutations. The children were from unrelated families. Urine and plasma glycerol levels were measured using a three-step enzymatic approach. Platelet morphology and function were studied using electron microscopy, aggregations, and adenosine triphosphate (ATP) secretion tests.


RESULTS
The index patients were homozygous for AQP7 G264V, which has previously been shown to inhibit transport of glycerol in Xenopus oocytes. We also detected a subclinical platelet secretion defect with reduced ATP secretion, and the absence of a secondary aggregation wave after epinephrine stimulation. Electron microscopy revealed round platelets with centrally located granules. Immunostaining showed AQP7 colocalization, with dense granules that seemed to be released after strong platelet activation. Healthy relatives of these patients, who were homozygous (not heterozygous) for G264V, also had hyperglyceroluria and platelet granule abnormalities.


CONCLUSIONS
The discovery of an association between urine glycerol loss and a platelet secretion defect is a novel one, and our findings imply the involvement of AQPs in platelet secretion. Additional studies are needed to define whether AQP7 G264V is also a risk factor for mental disability.
Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
Christophe
C
Goubau
Jaak
J
Jaeken
Elena N
EN
Levtchenko
Chantal
C
Thys
Michela
M
Di Michele
Geert A
GA
Martens
Erik
E
Gerlo
Rita
R
De Vos
Gunnar M
GM
Buyse
Nathalie
N
Goemans
Chris
C
Van Geet
Kathleen
K
Freson
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D051400:Aquaporin 3 / Q000235:genetics; D020346:Aquaporins / Q000235:genetics* / Q000378:metabolism; D001791:Blood Platelet Disorders / Q000235:genetics*; D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D003062:Codon; D005260:Female; D005990:Glycerol / Q000097:blood / Q000652:urine; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D021381:Protein Transport; D055815:Young Adult
C114141:AQP7 protein, human; C109669:AQP9 protein, human; D020346:Aquaporins; D003062:Codon; D051400:Aquaporin 3; D005990:Glycerol