Severe perinatal thrombosis in double and triple heterozygous offspring of a family segregating two independent protein S mutations and a protein C mutation

Molecular genetic and phenotypic analyses were performed in a highly unusual case of combined protein S and protein C deficiency manifesting in a family in which a child had died perinatally from renal vein thrombosis. Antenatal diagnosis in a second pregnancy was initially performed by indirect restriction fragment length polymorphism (RFLP) tracking using a neutral dimorphism within the PROS gene and served to exclude severe protein S deficiency. Am umbilical vein blood sample at 22 weeks gestation showed isolated protein C deficiency. This pregnancy proceeded to a full-term delivery without thrombotic complications. Molecular genetic analysis of the PROC and PROS gene segregating in the family then yielded one PROC gene lesion in the father and two PROS gene lesions, one in each parent. These lesions were shown to segregate with the respective deficiency states through the family pedigree. Analysis of DNA from paraffin-embedded liver tissue taken from the deceased child showed the presence of both PROS mutations, as well as the PROC mutation. Genotypic analysis of the second child showed a PROC mutation, but neither PROS mutation consistent with its possession of normal protein S levels and a low/borderline protein C level. Antenatal diagnosis was then performed in a third pregnancy by direct mutation detection. However, although the fetus carried only the paternal PROS and PROC gene lesions, the child developed renal thrombosis in utero. It may be that a further genetic lesion at a third locus still remains to be defined. Alternatively, the intrauterine development of thrombosis in this infant could have been caused, at least in part by a transplacental thrombotic stimulus arising in the protein S-deficient maternal circulation. This analysis may, therefore, serve as a warning against extrapolating too readily from genotype to phenotype in families with a complex thrombotic disorder.     

A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders

Innes AM, Boycott KM, Puffenberger EG, Redl D, MacDonald IM, Chudley AE, Beaulieu C, Perrier R, Gillan T, Wade A, Parboosingh JS. A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders. Bardet‐Biedl syndrome (BBS) is a multisystem genetically heterogeneous disorder, the clinical features of which are largely the consequence of ciliary dysfunction. BBS is typically inherited in an autosomal recessive fashion, and mutations in at least 14 genes have been identified. Here, we report the identification of a founder mutation in the BBS2 gene as the cause for the increased incidence of this developmental disorder in the Hutterite population. To ascertain the Hutterite BBS locus, we performed a genome‐wide single nucleotide polymorphism (SNP) analysis on a single patient and his three unaffected siblings from a Hutterite family. The analysis identified two large SNP blocks that were homozygous in the patient but not in his unaffected siblings, one of these regions contained the BBS2 gene. Sequence analysis and subsequent RNA studies identified and confirmed a novel splice site mutation, c.472‐2A>G, in BBS2. This mutation was also found in homozygous form in three subsequently studied Hutterite BBS patients from two different leuts, confirming that this is a founder mutation in the Hutterite population. Further studies are required to determine the frequency of this mutation and its role, if any, in the expression of other ciliopathies in this population.     

Horizontal and vertical ridge augmentation: a novel approach using osteosynthesis microplates, bone grafts, and resorbable barriers

A novel approach to augmenting alveolar ridges simultaneously with implant placement is presented. The technique is based on the use of custom-shaped osteosynthesis plates, which are fixed to the bone with miniscrews. The plates provide a rigid scaffolding for bone chips. Resorbable barriers are used to cover the plates and the grafts. The results of three selected cases are presented. This technique is relatively simple, can be used in almost any clinical situation, and can provide excellent results.     

What is the mechanism of flow‐mediated arterial dilatation

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Total cavopulmonary anastomosis using atrial septal flap: technique and early results

Introduction The Fontan procedure has undergone many modifications to avoid atrial arrhythmias and thrombus formation. We used patient’s interatrial septum as a flap to direct the inferior venacaval blood to the superior venacava. Methods Seventeen patients, aged 1 to 17 years, underwent modified total cavopulmonary anastomosis. Interatrial septum was used to create the inner half of the atrial tunnel, outer half being formed by right atrial free wall. Post-operatively, all patients underwent echocardiography. Seven patients underwent 24 hour ambulatory Holter monitoring and 6 patients underwent cardiac catheterization and cineangiography. Results There was one early death due to low cardiac output. One patient had transient supraventricular arrhythmia. Two patients had singnificant pleural effusion. Holter Monitoring reveled sinus rhythm in all 7 patients studied. Follow up ranged from 18 to 60 months and patients were evaluated as they came for follow up. Long term follow up is currently being compiled. There was one late death from a non-cardiac cause. The remaining patients were in New York Heart Association (NYHA) Class I or II. All patients were in sinus rhythm. Echocardiography and cineangiography revealed absence of obstruction or leak. Conclusions Total cavopulmonary anastomosis using autogenous atrial septum is a useful modification for classical cavopulmonary anastomosis and provides good early results.     

Continuous pH monitoring in wounds using a composite indicator dressing — A feasibility study

PurposeModern burn care strives for new means to guarantee optimised wound healing. Several studies have shown a correlation between the pH value in a (burn) wound and successful wound healing. A multitude of devices to monitor pH is available, all requiring direct wound contact and removal of the dressing for pH monitoring. The aim of this feasibility study was to create a sterile and easy to handle method for pH monitoring while simultaneously using an advanced wound dressing.Materials and methodsDressing sheets of biotechnologically generated nanofibrillar cellulose (epicite^hydro) were chemically functionalised with the indicator dye GJM-534. pH-donors with increasing pH were subsequently applied to the created indicator dressing. To investigate temporal resolution and continuous monitoring we used circular pH-donors with different pH (7 and 10) and decreasing diameters that were placed on another dressing sheet. Clinically relevant spatial resolution was checked by a wound bed simulation with small areas (8 mm) of higher pH (10) on a field of lower pH (7) and vice versa.ResultsThe indicator dressing showed a gradual colouring from yellow to dark orange with increasing pH in steps of 0.3. After conversion of digital pictures to greyscale values, a sigmoidal distribution with a pK_a-value of 8.4 was obtained. A ring-like pattern with alternating colour change corresponding to the pH was observed in the continuous monitoring experiment and the wound bed simulation delivered excellent local resolution.ConclusionSince the pH of a (burn) wound can have a significant influence on wound healing, a pH indicator was successfully linked to an advanced, temporary, alloplastic wound dressing material. We were able to show the possibility of pH monitoring by the dressing itself. Additional testing, including studies with large case numbers for optimisation are necessary before clinical implementation.