Text Box: PHENOTYPE ANALYSIS OF DELETION 22q11.2 SYNDROME
PATIENTS WITH GPIb-β HEMIZYGOSITY
Kato T1, Kosaka K1, Kimura M1, Imamura S2, Yamada O3, Iwai K4, 
Takao A1, Momma K1, Matsuoka R1
1Department of Pediatric Cardiology, 2Research Division, The Heart Institute of Japan, 3Department of Hematology, 4Department of Neuropsychiatry, Tokyo Women’s Medical University, Tokyo, Japan

Objective: Patients with deletion 22q11.2 syndrome are hemizygous for glycoprotein(GP) Ib-β, one of the disease genes of Bernard-Soulier syndrome(BSS). We analyzed the phenotype including thrombocytopenia and the protein levels of GPIb-βin patients with deletion 22q11.2 syndrome.
Methods: In 99 patients with deletion 22q11.2 syndrome (del+) and 124 patients with similar conotruncal heart anomalies but without deletion (del-), platelet count and other clinical manifestations were studied. In 38 del+ patients with thrombocytopenia, we sequenced GPIb-β in the remaining allele. In 12 del+ and 5 del- patients with thrombocytopenia, mean platelet volume and platelet function were determined. In these 17 patients, we quantified the protein levels of GPIb-β by Western blotting.
Results: The incidence of thrombocytopenia was higher in del+ patients than in del- patients. Del+ patients with thrombocytopenia tended to have large platelets and slightly decreased platelet agglutination to ristocetin, which was a similar phenotype to that of BSS. No mutation was found in the remaining allele of GPIb-β in 38 del+ patients. The protein levels of GPIb-β were reduced in 12 del+ patients with thrombocytopenia. In 99 del+ patients, 10 showed psychiatric disorders. Eight of 10 showed thrombocytopenia and 2 also showed mild thrombocytopenia.
Conclusions: Our results suggest that thrombocytopenia in patients with deletion 22q11.2 syndrome was affected by the decreased expression of GPIb-β due to the haploinsufficiency. Deletion 22q11.2 patients with thrombocytopenia require careful observation for psychiatric disorders.

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