Proteina C

Br J Haematol. 1993 Jun;84(2):285-9.

Symptomatic type II protein C deficiency caused by a missense mutation (Gly 381-->Ser) in the substrate-binding pocket.

Marchetti G, Patracchini P, Gemmati D, Castaman G, Rodeghiero F, Wacey A, Cooper DN, Tuddenham EG, Bernardi F.

Centro Studi Biochimici delle Patologie del Genoma Umano, Università di Ferrara, Italy.

A patient with recurrent deep vein thrombosis and heterozygous type II deficiency, characterized by reduced protein C activity in both amidolytic and clotting functional assays, was investigated by direct sequencing of PCR fragments derived from the coding portion of the protein C gene. AG (8856) to A transition was noted in the patient which was not present in healthy controls. This mutation is predicted to cause the substitution of Ser for Gly 381, an evolutionari'y conserved residue in the substrate binding pocket of serine-proteases (Gly 216, chymotrypsin numbering). A computer model of the structure of the serine-protease domain indicates that the properties of the altered protein C molecule can be explained on the basis of steric hindrance between the substituted serine and the substrate arginine side chains.

PMID: 8398832 [PubMed - indexed for MEDLINE]

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Br J Haematol. 1992 Jun;81(2):277-82.

Rapid detection of a protein C gene mutation present in the asymptomatic and not in the thrombosis-prone lineage.

Bernardi F, Patracchini P, Gemmati D, Boninsegna S, Guerra S, Legnani C, Ballerini G, Marchetti G.

Centro Studi Biochimici delle Patologie del Genoma Umano-Istituto di Chimica Biologica, Universita' di Ferrara, Italy.

The presence of mutations in the serine protease domain of protein C was investigated by temperature gradient gel electrophoresis of PCR products in five patients with protein C deficiency and thrombosis. Molecules with an altered melting behaviour were detected in one subject with a history of venous and arterial thrombosis. Direct sequencing showed that a G deletion, present in the heterozygous state, caused a reading frame shift at Trp 300 and subsequently a premature termination at the codon 335. The resulting suppression of the protein C catalytic function explains the reduction of protease activity to half. In addition the mutation caused a reduction of the antigen level in plasma. Temperature gradient gel electrophoresis enabled the rapid detection of the gene alteration in the family of the propositus. Several members of the paternal lineage had had severe thrombotic episodes. Unexpectedly the mutation was found to be inherited from the clinically asymptomatic maternal lineage, thus suggesting that an additional unknown defect from the paternal lineage is present in the thrombosis-prone propositus.

PMID: 1643025 [PubMed - indexed for MEDLINE]

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Hum Genet. 1989 Jan;81(2):191-2.

Sublocalization of the human protein C gene on chromosome 2q13-q14.

Patracchini P, Aiello V, Palazzi P, Calzolari E, Bernardi F.

Centro Studi Biochimici sul Morbo di Cooley, Università di Ferrara, Italy.

The localization of human protein C gene on chromosome 2 was investigated by in situ hybridization using a partial cDNA for protein C. Silver-grain analysis indicates that the protein C gene is located on 2q13-q14.

PMID: 2912888 [PubMed - indexed for MEDLINE]