Congenital macrothrombocytopenia is a heterogeneous disorder in India.
BACKGROUND
Inherited macrothrombocytopenia represents a heterogeneous group of disorders which are characterized by the presence of a reduced number of abnormally large platelets in the circulation, which may or may not be associated with a bleeding tendency. In spite of several causative genes having been identified, the underlying genetic defects remain to be identified in approximately half of the cases.


OBJECTIVE
To understand the molecular pathology of isolated giant platelet disorder from India.


METHODS
We studied 112 cases that were referred for investigation of macrothrombocytopenia. Agonist induced platelet aggregation and platelet GP1b/IX/V receptor expression were investigated to assess GP1b/IX/V receptor expression and the GP1BA, GP1BB, GP9, ABCG5, ABCG8, TUBB1 and MYH9 genes were analysed to identify candidate gene defects.


RESULTS
Twenty-three candidate gene defects were identified in 48 of 112 cases, 20 of which were novel. Of the candidate defects identified, 91% were missense and 9% were nonsense variations. The missense variations were in GP9 (9), ABCG5 (4), GP1BB (3), GP1BA (3) and MYH9 (2), while the nonsense defects occurred in MYH9 (1) and GP1BA (1).


CONCLUSIONS
This study increases the understanding of the molecular basis of an isolated giant platelet disorder, a common heterogeneous condition prevalent in north and eastern India.
Department of Haemostasis and Thrombosis, National Institute of Immunohaematology, Parel, Mumbai.
S
S
Ali
Surat Raktadan Kendra, Surat, Gujarat, India.
K
K
Ghosh
Department of Cardiovascular Science, Medical School, University of Sheffield, Sheffield, UK.
M E
ME
Daly
Department of Cardiovascular Science, Medical School, University of Sheffield, Sheffield, UK.
D J
DJ
Hampshire
Department of Cardiovascular Science, Medical School, University of Sheffield, Sheffield, UK.
M
M
Makris
Department of Haematology, NRS Medical College and Hospital, Kolkata, India.
M
M
Ghosh
Department of Haematology, NRS Medical College and Hospital, Kolkata, India.
L
L
Mukherjee
Department of Haematology, NRS Medical College and Hospital, Kolkata, India.
M
M
Bhattacharya
Department of Haemostasis and Thrombosis, National Institute of Immunohaematology, Parel, Mumbai.
S
S
Shetty
D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5 / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D002648:Child; D018389:Codon, Nonsense; D005260:Female; D056726:Genetic Association Studies; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis* / Q000235:genetics; D005838:Genotype; D006470:Hemorrhage / Q000209:etiology; D006579:Heterozygote; D006801:Humans; D007194:India; D008074:Lipoproteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000235:genetics; D020125:Mutation, Missense; D018995:Myosin Heavy Chains / Q000235:genetics; D010641:Phenotype; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D013921:Thrombocytopenia / Q000151:congenital / Q000175:diagnosis* / Q000235:genetics; D055815:Young Adult
C416945:ABCG5 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018389:Codon, Nonsense; D008074:Lipoproteins; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor; D018995:Myosin Heavy Chains
GP1b/IX/V complex; MYH9; giant platelet disorder; macrothrombocytopenia; thrombocytopenia