Helmut Mair - Academia.edu (original) (raw)

Papers by Helmut Mair

Journal of cardiothoracic surgery, Apr 18, 2024

The Thoracic and Cardiovascular Surgeon, 2006

One cause of diffuse bleeding after cardiac operations may be a low plasma concentration of coagu... more One cause of diffuse bleeding after cardiac operations may be a low plasma concentration of coagulation Factor XIII, which is essential for coagulation but is not covered by standard coagulation monitoring. In a prospective, randomized, double blinded study, 2500 units, 1250 units, and a placebo were administered in groups of 25 patients each, immediately after administration of protamine. Postoperative amount of blood loss and blood transfusion was recorded. Patients were not statistically different with respect to the course of plasma levels of Factor XIII until administration of the study drug. In all groups Factor XIII fell from preoperative normal values to subnormal values after extracorporeal circulation. After administration of the study drug, Factor XIII increased to 71 %, 85 %, 103 % in the placebo, 1250 units, and 2500 units group, respectively, and these differences were statistically significant ( p < 0.05). Postoperative blood loss was lowest in the 2500 units group and highest in the placebo group, however this was not significantly different. There was also no significant difference in the amount of blood transfusion. After differentiating all patients according to their post medication Factor XIII level into two groups with levels of < 70 % and > or = 70 %, postoperative blood loss was found to be significantly higher in the < 70 % group as was the amount of blood transfusions. Factor XIII administration reduces postoperative blood loss and the extent of blood transfusion after coronary surgery, however administration is only helpful if plasma levels are below the normal value. Measurement of plasma levels is recommended before Factor XIII substitution.

The Annals of Thoracic Surgery, Nov 1, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

European Journal of Cardio-Thoracic Surgery, Oct 1, 2003

Objective: Radiofrequency or the use of microwave energy in combination with atrial size reductio... more Objective: Radiofrequency or the use of microwave energy in combination with atrial size reduction during open heart surgery have been reported to be effective in up to 75% in the treatment of permanent atrial fibrillation. However, no data from prospective randomized trials using microwave energy are available. Methods: Forty-three patients with permanent atrial fibrillation undergoing open-heart surgery were randomly stratified into treatment group receiving microwave ablation and atrial size reduction (n ¼ 24) or control group (n ¼ 19). Patients in either group were treated with amiodarone or sotalol for 3 months if sinus rhythm or any atrioventricular rhythm was successfully restored. Follow-up time points were at 3, 6 and 12 month after surgery. Results: In the treatment group 22 out of 24 patients (91,7%) were successfully converted to sinus rhythm by using intraoperative microwave ablation therapy whereas only six out of 19 (31.5%) patients converted to sinus rhythm directly after surgery. At 12-month follow-up there were still a significantly higher percentage of patients in the treatment group free from atrial fibrillation when compared to control (80 vs. 33.3%, P ¼ 0:036). Conclusion: The preliminary data from this first prospectively randomized trial indicate that microwave ablation combined with atrial size reduction is a safe and highly efficient treatment in permanent atrial fibrillation.

Thoracic and Cardiovascular Surgeon, Feb 9, 2006

The Thoracic and Cardiovascular Surgeon, 2006

The Thoracic and Cardiovascular Surgeon, 2004

Thoracic and Cardiovascular Surgeon, 2007

We developed a new fabrication technique for 3-dimensional scaffolds for tissue engineering of hu... more We developed a new fabrication technique for 3-dimensional scaffolds for tissue engineering of human heart valve tissue. A human aortic homograft was scanned with an X-ray computer tomograph. The data derived from the X-ray computed tomogram were processed by a computer-aided design program to reconstruct a human heart valve 3-dimensionally. Based on this stereolithographic model, a silicone valve model resembling a human aortic valve was generated. By taking advantage of the thermoplastic properties of polyglycolic acid as scaffold material, we molded a 3-dimensional scaffold for tissue engineering of human heart valves. The valve scaffold showed a deviation of only 8 3-4% in height, length and inner diameter compared with the homograft. The newly developed technique allows fabricating custom-made, patient-specific polymeric cardiovascular scaffolds for tissue engineering without requiring any suture materials.

Thoracic and Cardiovascular Surgeon, Jan 18, 2012

Springer eBooks, 1993

Limitierungen ergeben sich aus vier prinzipiellen Grunden (wobei die meisten Probleme multifaktor... more Limitierungen ergeben sich aus vier prinzipiellen Grunden (wobei die meisten Probleme multifaktoriell zusammengesetzt sind): 1. Chirurgisch-technisch; die Probleme sind hier vielfaltig, weswegen 4 Einzelbeispiele reprasentativ ausgewahlt wurden: Die Behandlung des hypoplastischen Linksherzsyndroms im Neugeborenenalter, Eingriffe im hohen Alter, der mechanische Herzklappenersatz und die Lungentransplantation. In der Herzchirurgie ist im Prinzip alles machbar, wenn auch oft nicht perfekt. 2. Logistische Begrenzungen bestehen durch lange Wartelisten im Kinder- und auch im Erwachsenen-Bereich. Diese Probleme sind z. T durch den Pflegemangel auf Intensivstationen bedingt. 3. Finanzielle Begrenzungen sollten in einem reichen Land wie Deutschland nur selten entstehen. Ein neues Gesundheitsstrukturgesetz muste kostendampfend und nicht nivellierend sein. 4. Ethische Begrenzungen; es sollte machbar sein, was menschlich sinnvoll erscheint. In extremen Fallen ist die Anhorung einer Kommission aus verschiedenen lokalen Fachkollegen notwendig.

The Thoracic and Cardiovascular Surgeon, 2005

Medicina

Background and Objectives: The hemoadsorption device CytoSorb® (CytoSorbents Inc., Princeton, NJ,... more Background and Objectives: The hemoadsorption device CytoSorb® (CytoSorbents Inc., Princeton, NJ, USA) has been shown to efficiently remove ticagrelor from whole blood in vitro. A promising clinical experience was made with the integration of the hemoadsorption cartridge on the cardiopulmonary bypass (CPB) circuit during cardiac surgery to reduce adverse events. Materials and Methods: In this report, we describe a novel approach using a new apheresis platform, PUR-01 (Nikkisio Co., Ltd., Tokyo, Japan), which was used as the extracorporeal circuit where CytoSorb® could be installed for the removal of ticagrelor during off-pump coronary artery bypass (OPCAB) procedures. Results: In a 74-year-old male (index case) with coronary artery disease and dual antiplatelet therapy, hemoadsorption was initiated with a skin incision for OPCAB surgery and was continued for 221 min to eliminate ticagrelor. The blood volume that had circulated through the CytoSorb® was 39.04 L in total. Thus far, th...

Reviews in Cardiovascular Medicine

Objectives: Postoperative atrial fibrillation (POAF) is a frequent complication following cardiac... more Objectives: Postoperative atrial fibrillation (POAF) is a frequent complication following cardiac surgery. This study examined the safety and efficacy of the new DefiPace TM system consisting of two bi-atrial temporary pacing and cardioversion electrodes, a ventricular electrode and the DefiPace TM device (combined external pacemaker and cardioverter) for low-energy atrial cardioversion. Methods: The temporary electrodes were placed on the left and right atrium during open heart surgery. Pacing thresholds and sensing were measured up to the 6th postoperative day. The satisfactory handling of the electrodes was measured with a visual analog scale (VAS) 1-10, with 10 being the best and 1 being the lowest. In case of POAF, R-wave synchronous low-energy shocks (0.5-10 J) were applied for cardioversion. Results: Temporary electrodes were implanted in 29 patients (age 65.6 ± 10.4 years; 21 males, 14 OPCAB, 15 on-pump cardiac operations). Left or right atrial pacing thresholds ranged from 1.9 ± 1.3 V/ms to 5.0 ± 3.3 V/ms and P-wave sensing from 0.9 ± 0.6 mV to 1.5 ± 0.7 mV. VAS for handling of electrodes: implantation 7.1 ± 0.8 and removal 8.4 ± 1.0. POAF was observed in four patients. Two patients had successful atrial cardioversion with 3.5 J and 4.5 J. One patient converted spontaneously, and one patient remained in PAOF. There were no device-related adverse events. Conclusions: The DefiPace TM system can be used safely in patients undergoing cardiac surgery.

The Thoracic and Cardiovascular Surgeon, 2006

The Journal of Heart and Lung Transplantation, 2008

Introduction: ABO-incompatible heart transplantation, traditionally contraindicated because of th... more Introduction: ABO-incompatible heart transplantation, traditionally contraindicated because of the risk of hyperacute rejection, has been used selectively in recent years. Infants have limited production of isohemagglutinins, which may lower the risk of hyperacute rejection. A large national database was used to analyze the effect of ABO incompatibility on outcomes after heart transplantation in infants. Methods: Heart transplant recipients aged younger than 1 year reported to the United Network for Organ Sharing from 1999 to 2007 were divided according to donor-recipient ABO incompatibility or compatibility. Outcomes included Kaplan-Meier survival and hyperacute rejection. Propensityadjusted Cox regression modeling was used to identify predictors of mortality. Results: Of 591 infants that underwent heart transplantation, 35 (6%) received allografts from ABOincompatible donors. ABO-incompatible recipients trended toward more congenital heart disease (71% vs 66%; p ϭ 0.06) and were less likely to have dilated cardiomyopathy (11% vs 29%; p ϭ 0.02). One ABO-incompatible infant had hyperacute rejection requiring retransplantation. No ABOincompatible infant and 2 ABO-compatible infants died from hyperacute rejection. Survival was similar at 3 years. Propensity-adjusted Cox regression analysis demonstrated that ABO-incompatibility did not predict mortality (hazard ratio, 3.61; 95% confidence interval, 0.26-49.0; p ϭ 0.33). Conclusion: ABO-incompatible heart transplantation can be performed safely in infants without greater incidence of hyperacute rejection. ABO-incompatible heart transplantation should be strongly considered in infants to maximize donor organ utilization and reduce waiting-list mortality.

Journal of Clinical Medicine

Background: The vascular access in transcatheter aortic valve replacement (TAVR) was initially do... more Background: The vascular access in transcatheter aortic valve replacement (TAVR) was initially dominated by a surgical approach. Meanwhile, percutaneous closure systems became a well-established alternative. The aim of this study was to compare the clinical outcome between the two approaches. Methods: In this retrospective study, we observed 787 patients undergoing a TAVR-Procedure between 2013 and 2019. Of those, 338 patients were treated with surgical access and 449 with the Perclose ProGlide™-System (Abbott, Chicago, IL, USA). According to the Bleeding Academic Research Consortium (BARC) and Valve Academic Research Consortium (VARC) criteria, the primary combined endpoints were defined. Results: Overall hospital mortality was 2.8% with no significant difference between surgical (3.8%) and percutaneous (2.2%) access (p = 0.182). Major vascular complications or bleeding defined as the primary combined endpoint was not significantly different in either group (Surgical group 5.3%, Pr...

The Annals of Thoracic Surgery

Human Mutation, 1998

Marfan Syndrome (MfS) is an autosomal dominant inherited connective tissue disorder with variable... more Marfan Syndrome (MfS) is an autosomal dominant inherited connective tissue disorder with variable phenotypic expression of cardiovascular, skeletal and ocular manifestations. Cardiovascular complications, such as aortic aneurysm and dissection drastically reduce life expectancy of individuals with MfS, whereas preventive surgery substantially improves the prognosis of these patients. A number of mutations in the fibrillin 1 (FBN1) gene associated with MfS have been identified to date, demonstrating considerable molecular heterogeneity. One region, however, located around exon 24, exhibits a striking clustering of mutations, which are associated with a severe, socalled neonatal form of MfS. Here we report the first mutation (G2950A) in exon 24 of the neonatal region of the FBN1 gene, associated with a classic MfS phenotype. The mutation leads to the subsitution of valin by isoleucin (V984I), both uncharged amino acids, which only differ in a single methyl group. This defect was identified in a proband with cardiovascular manifestations of MfS by SSCP analysis of PCR-amplified genomic DNA, direct PCR sequencing and RFLP analysis. The substitution was neither detected in the unaffected 4-year old daughter of the proband, nor in 3 of his healthy family members nor in 108 allels from control individuals, suggesting that this mutation is causative for MfS in the patient. Since no other family member of the proband is affected by MfS, the defect described is sporadic. In summary, we identified a novel defect in exon 24 of the neonatal region of the FBN1 gene in a patient with a classic phenotype of MfS, suggesting that conservative substitutions in this region may lead to a less severe phenotype of the disease. This finding further demonstrates the remarkable phenotypic heterogeneity associated with FBN1 mutations and stresses the significance of modifying genes and individual alterations in protein function for the pheontypic expression of the disease.

Klinik und Forschung in der Chirurgie unter dem Aspekt von Effizienz und Ökonomie, 1997

Journal of cardiothoracic surgery, Apr 18, 2024

The Thoracic and Cardiovascular Surgeon, 2006

One cause of diffuse bleeding after cardiac operations may be a low plasma concentration of coagu... more One cause of diffuse bleeding after cardiac operations may be a low plasma concentration of coagulation Factor XIII, which is essential for coagulation but is not covered by standard coagulation monitoring. In a prospective, randomized, double blinded study, 2500 units, 1250 units, and a placebo were administered in groups of 25 patients each, immediately after administration of protamine. Postoperative amount of blood loss and blood transfusion was recorded. Patients were not statistically different with respect to the course of plasma levels of Factor XIII until administration of the study drug. In all groups Factor XIII fell from preoperative normal values to subnormal values after extracorporeal circulation. After administration of the study drug, Factor XIII increased to 71 %, 85 %, 103 % in the placebo, 1250 units, and 2500 units group, respectively, and these differences were statistically significant ( p < 0.05). Postoperative blood loss was lowest in the 2500 units group and highest in the placebo group, however this was not significantly different. There was also no significant difference in the amount of blood transfusion. After differentiating all patients according to their post medication Factor XIII level into two groups with levels of < 70 % and > or = 70 %, postoperative blood loss was found to be significantly higher in the < 70 % group as was the amount of blood transfusions. Factor XIII administration reduces postoperative blood loss and the extent of blood transfusion after coronary surgery, however administration is only helpful if plasma levels are below the normal value. Measurement of plasma levels is recommended before Factor XIII substitution.

The Annals of Thoracic Surgery, Nov 1, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

European Journal of Cardio-Thoracic Surgery, Oct 1, 2003

Objective: Radiofrequency or the use of microwave energy in combination with atrial size reductio... more Objective: Radiofrequency or the use of microwave energy in combination with atrial size reduction during open heart surgery have been reported to be effective in up to 75% in the treatment of permanent atrial fibrillation. However, no data from prospective randomized trials using microwave energy are available. Methods: Forty-three patients with permanent atrial fibrillation undergoing open-heart surgery were randomly stratified into treatment group receiving microwave ablation and atrial size reduction (n ¼ 24) or control group (n ¼ 19). Patients in either group were treated with amiodarone or sotalol for 3 months if sinus rhythm or any atrioventricular rhythm was successfully restored. Follow-up time points were at 3, 6 and 12 month after surgery. Results: In the treatment group 22 out of 24 patients (91,7%) were successfully converted to sinus rhythm by using intraoperative microwave ablation therapy whereas only six out of 19 (31.5%) patients converted to sinus rhythm directly after surgery. At 12-month follow-up there were still a significantly higher percentage of patients in the treatment group free from atrial fibrillation when compared to control (80 vs. 33.3%, P ¼ 0:036). Conclusion: The preliminary data from this first prospectively randomized trial indicate that microwave ablation combined with atrial size reduction is a safe and highly efficient treatment in permanent atrial fibrillation.

Thoracic and Cardiovascular Surgeon, Feb 9, 2006

The Thoracic and Cardiovascular Surgeon, 2006

The Thoracic and Cardiovascular Surgeon, 2004

Thoracic and Cardiovascular Surgeon, 2007

We developed a new fabrication technique for 3-dimensional scaffolds for tissue engineering of hu... more We developed a new fabrication technique for 3-dimensional scaffolds for tissue engineering of human heart valve tissue. A human aortic homograft was scanned with an X-ray computer tomograph. The data derived from the X-ray computed tomogram were processed by a computer-aided design program to reconstruct a human heart valve 3-dimensionally. Based on this stereolithographic model, a silicone valve model resembling a human aortic valve was generated. By taking advantage of the thermoplastic properties of polyglycolic acid as scaffold material, we molded a 3-dimensional scaffold for tissue engineering of human heart valves. The valve scaffold showed a deviation of only 8 3-4% in height, length and inner diameter compared with the homograft. The newly developed technique allows fabricating custom-made, patient-specific polymeric cardiovascular scaffolds for tissue engineering without requiring any suture materials.

Thoracic and Cardiovascular Surgeon, Jan 18, 2012

Springer eBooks, 1993

Limitierungen ergeben sich aus vier prinzipiellen Grunden (wobei die meisten Probleme multifaktor... more Limitierungen ergeben sich aus vier prinzipiellen Grunden (wobei die meisten Probleme multifaktoriell zusammengesetzt sind): 1. Chirurgisch-technisch; die Probleme sind hier vielfaltig, weswegen 4 Einzelbeispiele reprasentativ ausgewahlt wurden: Die Behandlung des hypoplastischen Linksherzsyndroms im Neugeborenenalter, Eingriffe im hohen Alter, der mechanische Herzklappenersatz und die Lungentransplantation. In der Herzchirurgie ist im Prinzip alles machbar, wenn auch oft nicht perfekt. 2. Logistische Begrenzungen bestehen durch lange Wartelisten im Kinder- und auch im Erwachsenen-Bereich. Diese Probleme sind z. T durch den Pflegemangel auf Intensivstationen bedingt. 3. Finanzielle Begrenzungen sollten in einem reichen Land wie Deutschland nur selten entstehen. Ein neues Gesundheitsstrukturgesetz muste kostendampfend und nicht nivellierend sein. 4. Ethische Begrenzungen; es sollte machbar sein, was menschlich sinnvoll erscheint. In extremen Fallen ist die Anhorung einer Kommission aus verschiedenen lokalen Fachkollegen notwendig.

The Thoracic and Cardiovascular Surgeon, 2005

Medicina

Background and Objectives: The hemoadsorption device CytoSorb® (CytoSorbents Inc., Princeton, NJ,... more Background and Objectives: The hemoadsorption device CytoSorb® (CytoSorbents Inc., Princeton, NJ, USA) has been shown to efficiently remove ticagrelor from whole blood in vitro. A promising clinical experience was made with the integration of the hemoadsorption cartridge on the cardiopulmonary bypass (CPB) circuit during cardiac surgery to reduce adverse events. Materials and Methods: In this report, we describe a novel approach using a new apheresis platform, PUR-01 (Nikkisio Co., Ltd., Tokyo, Japan), which was used as the extracorporeal circuit where CytoSorb® could be installed for the removal of ticagrelor during off-pump coronary artery bypass (OPCAB) procedures. Results: In a 74-year-old male (index case) with coronary artery disease and dual antiplatelet therapy, hemoadsorption was initiated with a skin incision for OPCAB surgery and was continued for 221 min to eliminate ticagrelor. The blood volume that had circulated through the CytoSorb® was 39.04 L in total. Thus far, th...

Reviews in Cardiovascular Medicine

Objectives: Postoperative atrial fibrillation (POAF) is a frequent complication following cardiac... more Objectives: Postoperative atrial fibrillation (POAF) is a frequent complication following cardiac surgery. This study examined the safety and efficacy of the new DefiPace TM system consisting of two bi-atrial temporary pacing and cardioversion electrodes, a ventricular electrode and the DefiPace TM device (combined external pacemaker and cardioverter) for low-energy atrial cardioversion. Methods: The temporary electrodes were placed on the left and right atrium during open heart surgery. Pacing thresholds and sensing were measured up to the 6th postoperative day. The satisfactory handling of the electrodes was measured with a visual analog scale (VAS) 1-10, with 10 being the best and 1 being the lowest. In case of POAF, R-wave synchronous low-energy shocks (0.5-10 J) were applied for cardioversion. Results: Temporary electrodes were implanted in 29 patients (age 65.6 ± 10.4 years; 21 males, 14 OPCAB, 15 on-pump cardiac operations). Left or right atrial pacing thresholds ranged from 1.9 ± 1.3 V/ms to 5.0 ± 3.3 V/ms and P-wave sensing from 0.9 ± 0.6 mV to 1.5 ± 0.7 mV. VAS for handling of electrodes: implantation 7.1 ± 0.8 and removal 8.4 ± 1.0. POAF was observed in four patients. Two patients had successful atrial cardioversion with 3.5 J and 4.5 J. One patient converted spontaneously, and one patient remained in PAOF. There were no device-related adverse events. Conclusions: The DefiPace TM system can be used safely in patients undergoing cardiac surgery.

The Thoracic and Cardiovascular Surgeon, 2006

The Journal of Heart and Lung Transplantation, 2008

Introduction: ABO-incompatible heart transplantation, traditionally contraindicated because of th... more Introduction: ABO-incompatible heart transplantation, traditionally contraindicated because of the risk of hyperacute rejection, has been used selectively in recent years. Infants have limited production of isohemagglutinins, which may lower the risk of hyperacute rejection. A large national database was used to analyze the effect of ABO incompatibility on outcomes after heart transplantation in infants. Methods: Heart transplant recipients aged younger than 1 year reported to the United Network for Organ Sharing from 1999 to 2007 were divided according to donor-recipient ABO incompatibility or compatibility. Outcomes included Kaplan-Meier survival and hyperacute rejection. Propensityadjusted Cox regression modeling was used to identify predictors of mortality. Results: Of 591 infants that underwent heart transplantation, 35 (6%) received allografts from ABOincompatible donors. ABO-incompatible recipients trended toward more congenital heart disease (71% vs 66%; p ϭ 0.06) and were less likely to have dilated cardiomyopathy (11% vs 29%; p ϭ 0.02). One ABO-incompatible infant had hyperacute rejection requiring retransplantation. No ABOincompatible infant and 2 ABO-compatible infants died from hyperacute rejection. Survival was similar at 3 years. Propensity-adjusted Cox regression analysis demonstrated that ABO-incompatibility did not predict mortality (hazard ratio, 3.61; 95% confidence interval, 0.26-49.0; p ϭ 0.33). Conclusion: ABO-incompatible heart transplantation can be performed safely in infants without greater incidence of hyperacute rejection. ABO-incompatible heart transplantation should be strongly considered in infants to maximize donor organ utilization and reduce waiting-list mortality.

Journal of Clinical Medicine

Background: The vascular access in transcatheter aortic valve replacement (TAVR) was initially do... more Background: The vascular access in transcatheter aortic valve replacement (TAVR) was initially dominated by a surgical approach. Meanwhile, percutaneous closure systems became a well-established alternative. The aim of this study was to compare the clinical outcome between the two approaches. Methods: In this retrospective study, we observed 787 patients undergoing a TAVR-Procedure between 2013 and 2019. Of those, 338 patients were treated with surgical access and 449 with the Perclose ProGlide™-System (Abbott, Chicago, IL, USA). According to the Bleeding Academic Research Consortium (BARC) and Valve Academic Research Consortium (VARC) criteria, the primary combined endpoints were defined. Results: Overall hospital mortality was 2.8% with no significant difference between surgical (3.8%) and percutaneous (2.2%) access (p = 0.182). Major vascular complications or bleeding defined as the primary combined endpoint was not significantly different in either group (Surgical group 5.3%, Pr...

The Annals of Thoracic Surgery

Human Mutation, 1998

Marfan Syndrome (MfS) is an autosomal dominant inherited connective tissue disorder with variable... more Marfan Syndrome (MfS) is an autosomal dominant inherited connective tissue disorder with variable phenotypic expression of cardiovascular, skeletal and ocular manifestations. Cardiovascular complications, such as aortic aneurysm and dissection drastically reduce life expectancy of individuals with MfS, whereas preventive surgery substantially improves the prognosis of these patients. A number of mutations in the fibrillin 1 (FBN1) gene associated with MfS have been identified to date, demonstrating considerable molecular heterogeneity. One region, however, located around exon 24, exhibits a striking clustering of mutations, which are associated with a severe, socalled neonatal form of MfS. Here we report the first mutation (G2950A) in exon 24 of the neonatal region of the FBN1 gene, associated with a classic MfS phenotype. The mutation leads to the subsitution of valin by isoleucin (V984I), both uncharged amino acids, which only differ in a single methyl group. This defect was identified in a proband with cardiovascular manifestations of MfS by SSCP analysis of PCR-amplified genomic DNA, direct PCR sequencing and RFLP analysis. The substitution was neither detected in the unaffected 4-year old daughter of the proband, nor in 3 of his healthy family members nor in 108 allels from control individuals, suggesting that this mutation is causative for MfS in the patient. Since no other family member of the proband is affected by MfS, the defect described is sporadic. In summary, we identified a novel defect in exon 24 of the neonatal region of the FBN1 gene in a patient with a classic phenotype of MfS, suggesting that conservative substitutions in this region may lead to a less severe phenotype of the disease. This finding further demonstrates the remarkable phenotypic heterogeneity associated with FBN1 mutations and stresses the significance of modifying genes and individual alterations in protein function for the pheontypic expression of the disease.

Klinik und Forschung in der Chirurgie unter dem Aspekt von Effizienz und Ökonomie, 1997