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Bernard–Soulier syndrome in a patient doubly heterozygous for two frameshift mutations in the glycoprotein Ibα gene
Author(s) -
AfsharKharghan Vahid,
Craig Fiona E.,
López José A.
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2000.02261.x
Subject(s) - frameshift mutation , bernard–soulier syndrome , genetics , allele , biology , haplotype , stop codon , compound heterozygosity , mutation , gene , microbiology and biotechnology , glycoprotein
We report here the genetic basis of Bernard–Soulier syndrome in a compound heterozygote for two mutant glycoprotein (GP) Ibα alleles. One allele contained a novel four base‐pair deletion (TGAG) that eliminated the last base of the codon for Ser39 (AGT) and the entire codon for Glu40 (GAG), causing a reading frame shift that yielded a stretch of 51 amino acids before a premature stop codon. The other allele also contained a frame‐shift mutation, caused by deletion of the last two bases of the codon for Tyr492 (TAT). This allele produced a truncated glycoprotein Ibα that, although not expressed on the surface of the patient's platelets, was detectable in the plasma. The second allele has been identified previously by our group and other investigators as the cause of Bernard–Soulier syndrome in patients of northern European ancestry. This allele carried a haplotype identical to those of the previously reported cases, with the following polymorphic markers: two tandem repeats in the VNTR region, C at nucleotide −5 from the ATG start codon and a substitution of G for A in the third base for codon Arg342. These findings suggest that this particular Bernard–Soulier mutation occurred once on the background of a rare haplotype and has spread throughout the northern European population.