A 5.3-kb deletion including exon XIII of the protein S alpha gene occurs in
two protein S-deficient families [see comments]
DK Schmidel, RM Nelson, EH Broxson , PC Comp, RA Marlar and GL Long
Department of Biochemistry, University of Vermont, Burlington 05405.
Genomic DNA samples from 12 protein S-deficient families with hereditary
thrombophilia were analyzed by Southern hybridization using protein S cDNA
probes. Protein S-deficient members of families A and B possessed identical
restriction fragment length polymorphisms, which suggest the absence of 5.3
kb from one of their protein S alpha alleles. The abnormal alleles from
individuals A7 and B1 were amplified by the polymerase chain reaction using
a forward primer in intron K and a reverse primer in exon XIV. The
amplified DNA was cloned and sequenced. Sequence comparison with the normal
protein S alpha gene showed that most of intron L (roughly 4.7 kb), the
entire exon XIII (151 bp), and about a quarter of intron M (407 bp) were
missing from both the A7 and B1 clones. Exon XIII contains all three
potential N- glycosylation sites in human protein S. This deletion may
result in RNA transcripts in which exon XII is spliced to exon XIV. Such an
arrangement would generate a stop codon at position 463 and consequently
produce a nonglycosylated protein S molecule truncated by 173 amino acids.
Volume 77,
Issue 3,
pp. 551-559,
02/01/1991
Copyright © 1991 by The American Society of Hematology
