Gross deletions-duplications in PROS1 are relatively common in point mutation-negative hereditary protein S deficiencyReportar como inadecuado

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Human Genetics

, Volume 126, Issue 3, pp 449–456

First Online: 23 May 2009Received: 23 March 2009Accepted: 14 May 2009


Hereditary protein S PS deficiency is an autosomal disorder caused by mutations in the PS gene PROS1. Conventional PCR-based mutation detection identifies PROS1 point mutations in approximately 50% of the cases. To verify if gross copy number variations CNVs are often present in point mutation-negative hereditary PS deficiency we used multiplex ligation-dependent probe amplification MLPA as a detection tool in samples from individuals with a high probability of having true PS deficiency. To this end, DNA samples from nine PS deficient probands with family members seven type I and two type III and nine isolated probands three type I and six type III, in whom PROS1 mutations were not found by DNA sequencing, were evaluated. An independent quantitative PCR qPCR was performed to confirm the findings of the MLPA assay. Family members were also tested when DNA was available. Gross abnormalities of PROS1 were found in six out of eighteen probands. In three probands complete deletion of the gene was detected. Two probands had a partial deletion involving different parts of the gene one from exon 4 through 9 and another from exon 9 through 11. One family showed a duplication of part of PROS1. qPCR analysis was in accordance with these results. In conclusion, this study substantiates that gross gene abnormalities in PROS1 are relatively common in hereditary PS deficient patients and that MLPA is a useful tool for direct screening of CNVs in PROS1 point mutation-negative individuals.

M. C. Pintao and A. A. Garcia contributed equally to this article.

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Autor: Maria C. Pintao - A. A. Garcia - D. Borgel - M. Alhenc-Gelas - C. A. Spek - M. C. H. de Visser - S. Gandrille - Piete


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