A 5.3-kb deletion including exon XIII of the protein S alpha gene occurs in two protein S-deficient families.
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.
Schmidel
D K
DK
Department of Biochemistry, University of Vermont, Burlington 05405.
Nelson
R M
RM
Broxson
E H
EH
Comp
P C
PC
Marlar
R A
RA
Long
G L
GL
D000483:Alleles; D001483:Base Sequence; D015139:Blotting, Southern; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D005091:Exons; D005784:Gene Amplification / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017293:Protein S; D013927:Thrombosis / Q000235:genetics
D006023:Glycoproteins; D017293:Protein S