Linkage of four polymorphisms on the α<sub>IIb</sub> gene

Ruan,; Peyruchaud, Olivier; Nurden,; Bourre,

doi:10.1046/j.1365-2141.1998.00810.x

Cited by 15 publications

(13 citation statements)

References 13 publications

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“…T in exon 30 were in complete linkage disequilibrium. This was previously reported along with a fourth polymorphism involving a 9-bp deletion in intron 21 [23].…”

Section: Discussionmentioning

confidence: 74%

Novel mutations in GP IIb gene in Glanzmann's thrombasthenia from India

Vijapurkar

Ghosh²,

Shetty

2009

Platelets

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The integrin GPIIb-IIIa plays an important role in platelet activation and plug formation. Quantitative and qualitative dysfunction in this receptor causes Glanzmann's thrombasthenia (GT) and leads to a bleeding tendency. Mutations in the GPIIb or GPIIIa gene are known to be responsible for the inherited form of this disease, which is characterized by mucocutaneous bleeding and other clinically severe bleeding manifestations. GT is an autosomal inherited platelet function. Mutations in the GPIIIa gene but not GPIIb gene in GT patients from Western India have been studied. Hence, this study was designed and included for the first time two mutation detection strategies: single strand conformation polymorphism and conformation sensitive gel electrophoresis followed by sequencing. Patients diagnosed as GT in our laboratory were screened for mutations. We report 12 mutations in 13 patients, of which 11 are novel mutations. Six mutations were missense, four were deletions and two were splice junction mutations. The study thus identifies novel mutations in the GPIIb gene in patients from Western India, implicating the importance of certain amino acids in structure-function correlations as well as enabling prenatal diagnosis in these families.

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“…T in exon 30 were in complete linkage disequilibrium. This was previously reported along with a fourth polymorphism involving a 9-bp deletion in intron 21 [23].…”

Section: Discussionmentioning

confidence: 74%

Novel mutations in GP IIb gene in Glanzmann's thrombasthenia from India

Vijapurkar

Ghosh²,

Shetty

2009

Platelets

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“…The patient was found to be heterozygote for HPA‐3a/HPA‐3b. The differences for the fragments containing exon 22 and exon 30 corresponded to two new silent polymorphisms which are also linked to the HPA‐3 system ( Ruan et al , 1998 ). In contrast, the two altered patterns seen for fragments containing exon 12 and exon 18 did not correspond to any known polymorphisms of the GPIIb gene.…”

Section: Resultsmentioning

confidence: 99%

Double heterozygosity of the GPIIb gene in a Swiss patient with Glanzmann's thrombasthenia

et al. 1998

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Glanzmann's thrombasthenia (GT) results from a qualitative or quantitative defect of GPIIb–IIIa complexes (integrin αIIbβ3), the fibrinogen receptor on platelets. This integrin plays a critical role in platelet aggregation. In this report we describe the molecular abnormalities of a patient with clinical and laboratory findings typical of type I Glanzmann's thrombasthenia. SDS‐PAGE with Western blotting revealed an absence of GPIIb but small amounts of normally migrating GPIIIa in his platelets. A non‐radioactive PCR‐SSCP procedure and direct sequence analysis of PCR‐amplified DNA fragments showed the patient to be a compound heterozygote for mutations in the GPIIb gene. A single point mutation (G to A) at nucleotide 1064 of the cDNA derived from the mother's allele led to a Glu324 to Lys amino acid substitution in GPIIb. It was responsible for a MscI restriction site in exon 12 of the GPIIb gene. This amino acid substitution changes the electric charge between the second and third Ca++‐binding domains of GPIIb. The second mutation was inherited from his father and is in exon 18 of the GPIIb gene. It was a T → C base transition at position 1787 of GPIIb cDNA and results in a Ile565 to Thr substitution. The two GPIIb mutations identified in this study will provide new information on GPIIb–IIIa structure and biosynthesis.

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“…The first four variants have already been reported to be reciprocally linked and found in homozygosis in individuals with normal platelet aggregation responses. 24 Exon-trapping analysis of a genomic DNA fragment containing the variant intron 21 indicated that it does not have a significant impact on αIIb gene expression at the transcription level. Both alleles generated similar amounts of transcripts, but a scarce additional RT-PCR product was obtained from the variant αIIb allele (Online Supplementary Figure S1B).…”

Section: Identification Of the L718p Mutation In β3mentioning

confidence: 99%