Espinosa-Parrilla Y, Morell M, Souto J C, Tirado I, Fontcuberta J, Estivill X, Sala N
Departament de Genètica Mèdica i Molecular, Institut de Recerca Oncològica, Barcelona, Spain.
Hum Mutat. 1999;14(1):30-9. doi: 10.1002/(SICI)1098-1004(1999)14:1<30::AID-HUMU4>3.0.CO;2-X.
DNA sequence analysis of the protein S gene (PROS1) in 22 Spanish probands with type I or III PS deficiency, has allowed the identification of 10 different mutations and 2 new sequence variants in 15 probands. Nine of the mutations, 8 of which are novel, cosegregate with type I or quantitative PS deficiency in 12 of the 13 pedigrees analyzed. One of these mutations (Q238X) also cosegregates with both type I and III PS-deficient phenotypes coexisting in a type I/III pedigree. Another mutation identified in a pedigree with these two PS phenotypes is the missense mutation R520G, present in the homozygous form in the type I propositus and in the heterozygous form in his type III relatives. By contrast, no cosegregating PROS1 mutation has been found in any of the six families with only type III phenotypes. Three of these families, as well as the two families with type I and I/III phenotypes where no other PROS1 mutation has been identified, segregate the P allele of the S460P variant, although this allele does not always cosegregate with the deficient phenotype. From these results we conclude that while mutations in PROS1 are the main cause of type I PS deficiency, the molecular basis of the type III phenotype is probably more complex, with many cases not being explained by a PROS1 mutation.
对22名患有I型或III型蛋白S缺乏症（PS缺乏症）的西班牙先证者的蛋白S基因（PROS1）进行DNA序列分析，已在15名先证者中鉴定出10种不同的突变和2种新的序列变异。其中9种突变，其中8种是新发现的，在13个分析的家系中的12个家系中与I型或定量PS缺乏症共分离。这些突变之一（Q238X）也与I/III型家系中同时存在的I型和III型PS缺乏表型共分离。在具有这两种PS表型的家系中鉴定出的另一种突变是错义突变R520G，在I型先证者中以纯合形式存在，在其III型亲属中以杂合形式存在。相比之下，在仅具有III型表型的六个家族中的任何一个中均未发现共分离的PROS1突变。其中三个家族，以及未鉴定出其他PROS1突变的具有I型和I/III型表型的两个家族，分离出S460P变体的P等位基因，尽管该等位基因并不总是与缺陷表型共分离。从这些结果我们得出结论，虽然PROS1突变是I型PS缺乏症的主要原因，但III型表型的分子基础可能更复杂，许多病例无法用PROS1突变来解释。
