Milen Minkov1,2,3, Petra Zeitlhofer4, Andreas Zoubek5, Leo Kager3, Simon Panzer6, Oskar A Haas3,4. 1. Department of Pediatrics, Clinic Floridsdorf, Vienna, Austria. 2. Faculty of Medicine, Sigmund Freud University, Vienna, Austria. 3. St. Anna Children's Hospital, Department of Pediatric Hematology/Oncology, University Clinic of Pediatrics, Medical University of Vienna, Vienna, Austria. 4. Labdia GmbH, St. Anna Kinderkrebsforschung GmbH, Vienna, Austria. 5. Private Practice for General Pediatrics and Pediatric Hematology/Oncology, Maria Enzersdorf, Austria. 6. Department of Blood Group Serology and Transfusion Medicine, Medical University Vienna, Vienna, Austria.
Abstract
Background: Bernard-Soulier Syndrome (BSS) is a rare autosomal recessive bleeding disorder with large platelets and thrombocytopenia. It is caused by homozygous or compound heterozygous mutations in the GP1BA, GP1BB, or GP9 genes, which together encode the platelet surface receptor glycoprotein complex GPIb-IX-V. Objectives: We report two novel heterozygous mutations in the GP1BA and the GP9 genes, respectively. Patients/ Methods: We analyzed the platelet glycoprotein expression by flow cytometry and screened the relevant genes for responsible mutations in two unrelated families. Results: Flow cytometric analyses revealed the absence of CD42a (GPIX) and CD42b (GPIb) on the platelets in the two affected siblings of family 1 and a significantly reduced expression of CD42b (GPIb) in the patient of family 2. In the two siblings, we identified a known frameshift (c.1601_1602delAT) and a novel nonsense mutation (c.1036C>T) in the GP1BA gene that abrogated the production of GP1bα. In the other patient, we found a novel missense mutation (c.112T>C) that was co-inherited with a common one (c.182A>G) in the GP9 gene, respectively. All analyzed heterozygous carriers were asymptomatic and had a normal GPIb-IX-V expression. Conclusions: The two novel GP1BA and GP9 mutations reported herein increment the number of causative genetic defects in BSS.
Background: Bernard-Soulier Syndrome (BSS) is a rare autosomal recessive bleeding disorder with large platelets and thrombocytopenia. It is caused by homozygous or compound heterozygous mutations in the GP1BA, GP1BB, or GP9 genes, which together encode the platelet surface receptor glycoprotein complex GPIb-IX-V. Objectives: We report two novel heterozygous mutations in the GP1BA and the GP9 genes, respectively. Patients/ Methods: We analyzed the platelet glycoprotein expression by flow cytometry and screened the relevant genes for responsible mutations in two unrelated families. Results: Flow cytometric analyses revealed the absence of CD42a (GPIX) and CD42b (GPIb) on the platelets in the two affected siblings of family 1 and a significantly reduced expression of CD42b (GPIb) in the patient of family 2. In the two siblings, we identified a known frameshift (c.1601_1602delAT) and a novel nonsense mutation (c.1036C>T) in the GP1BA gene that abrogated the production of GP1bα. In the other patient, we found a novel missense mutation (c.112T>C) that was co-inherited with a common one (c.182A>G) in the GP9 gene, respectively. All analyzed heterozygous carriers were asymptomatic and had a normal GPIb-IX-V expression. Conclusions: The two novel GP1BA and GP9 mutations reported herein increment the number of causative genetic defects in BSS.
Authors: Hai Po Helena Liang; Marie-Christine Morel-Kopp; Jeannine M Clemetson; Kenneth J Clemetson; Riitta Kekomaki; Hartmut Kroll; Katerina Michaelides; Edward G D Tuddenham; Karen Vanhoorelbeke; Christopher M Ward Journal: Thromb Haemost Date: 2005-09 Impact factor: 5.249
Authors: Magdalena Skalníková; Kateřina Staňo Kozubík; Jakub Trizuljak; Zuzana Vrzalová; Lenka Radová; Kamila Réblová; Radka Holbová; Terézia Kurucová; Hana Svozilová; Jiří Štika; Ivona Blaháková; Barbara Dvořáčková; Marie Prudková; Olga Stehlíková; Michal Šmída; Leoš Křen; Petr Smejkal; Šárka Pospíšilová; Michael Doubek Journal: Int J Mol Sci Date: 2022-01-14 Impact factor: 5.923