title: The molecular genetic basis of Glanzmann's thrombasthenia in a gypsy population in France: identification of a new mutation on the alpha IIb gene.
abstract: Glanzmann's thrombasthenia is a rare inherited bleeding disorder caused by a qualitative or quantitative defect of platelet alpha IIb beta 3. We describe here a new mutation that is the molecular genetic basis of Glanzmann's thrombasthenia in two gypsy families. Our investigation was focused on the alpha IIb gene as a result of biochemical and immunologic analysis of patients' platelets showing undetectable alpha IIb but residual beta 3 levels. The entire alpha IIb cDNA was polymerase chain reaction (PCR) amplified using patients platelet RNA. Sequence analysis showed an 8-bp deletion located at the 3' end of exon 15. This deletion causes a reading-frame shift leading to a premature stop codon and the synthesis of a severely truncated form of alpha IIb. Genomic DNA study showed a G-->A substitution, the Gypsy mutation, at the splice donor site of intron 15. This mutation results in an abnormal splicing occurring at an alternative donor site located 8 bp upstream from the mutation. Based on those results, an allele-specific PCR analysis was developed to allow a rapid identification of the mutation in patients and potential carriers of the gypsy community. This PCR analysis can also be used for genetic counseling and antenatal diagnosis.
authors.affiliation: Service d'Hématologie Biologique, Hôpital Robert Debré, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Schlegel
authors.forename: O
authors.initials: O
authors.lastname: Gayet
authors.forename: M C
authors.initials: MC
authors.lastname: Morel-Kopp
authors.forename: B
authors.initials: B
authors.lastname: Wyler
authors.forename: M F
authors.initials: MF
authors.lastname: Hurtaud-Roux
authors.forename: C
authors.initials: C
authors.lastname: Kaplan
authors.forename: J
authors.initials: J
authors.lastname: Mc Gregor
mesh_terms: D000483:Alleles; D001483:Base Sequence; D001792:Blood Platelets / Q000502:physiology; D017931:DNA Primers / Q000737:chemistry; D005006:Ethnicity; D005260:Female; D005602:France; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D013915:Thrombasthenia / Q000235:genetics*
chemical_list: D017931:DNA Primers; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger