Distribution of PROS mutations associated with quantitative and qualitative PS deficiency. The domain structure of PS is shown at the top of the figure, and the color coding indicates the corresponding exon encoding each protein domain. The numbers inside squares, diamonds, triangles, and circles denote the numbers of different missense, frameshift, nonsense, and splice site mutations, respectively, for each PS domain. (A) Mutations causing quantitative PS deficiency are distributed throughout the PROS. Data source available from heterozygous, homozygous, and compound heterozygous states compiled by Gandrille et al⁸  and from 19 new mutations recently published after a Medline search (key words: protein S, mutations) between July 1999 and September 2002. (B) Mutations causing qualitative PS deficiency tend to locate in the Gla and EGF-like domains of the PROS. AS indicates aromatic stack; TSR, thrombin-sensitive region; EGF, epidermal growth factor–like domain; LGR; laminin-G type repeat.