F H Herrmann

University of Costa Rica, San José, San José, Costa Rica

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Publications (119)350.6 Total impact

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    ABSTRACT: Background/aims: The application of intranasal oxytocin enhances facial emotion recognition in normal subjects and in subjects with autism spectrum disorders (ASD). In addition, various features of social cognition have been associated with variants of the oxytocin receptor gene (OXTR). Therefore, we tested for associations between mind-reading, a measure for social recognition and OXTR polymorphisms. Methods: 76 healthy adolescents and young adults were tested for associations between OXTR rs53576, rs2254298, rs2228485 and mind-reading using the "Reading the Mind in the Eyes Test" (RMET). Results: After Bonferroni correction for multiple comparisons, rs2228485 was associated with the number of incorrect answers when subjects evaluated male faces (P =0.000639). There were also associations between OXTR rs53576, rs2254298 and rs2228485 and other RMET dimensions according to P <0.05 (uncorrected). Conclusion: This study adds further evidence to the hypothesis that genetic variations in the OXTR modulate mind-reading and social behaviour.
    Nordic journal of psychiatry 07/2012; · 0.99 Impact Factor
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    ABSTRACT: Haemophilia A (HA) is X-chromosome linked bleeding disorders caused by deficiency of the coagulation factor VIII (FVIII). It is caused by FVIII gene intron 22 inversion (Inv22) in approximately 45% and by intron 1 inversion (Inv1) in 5% of the patients. Both inversions occur as a result of intrachromosomal recombination between homologous regions, in intron 1 or 22 and their extragenic copy located telomeric to the FVIII gene. The aim of this study was to analyze the presence of these mutations in 25 HA Costa Rican families. Patients, methods: We studied 34 HA patients and 110 unrelated obligate members and possible carriers for the presence of Inv22or Inv1. Standard analyses of the factor VIII gene were used incl. Southern blot and long-range polymerase chain reaction for inversion analysis. Results: We found altered Inv22 restriction profiles in 21 patients and 37 carriers. It was found type 1 and type 2 of the inversion of Inv22. During the screening for Inv1 among the HA patient, who were Inv22 negative, we did not found this mutation. Discussion: Our data highlight the importance of the analysis of Inv22 for their association with development of inhibitors in the HA patients and we are continuous searching of Inv1 mutation. This knowledge represents a step for genetic counseling and prevention of the inhibitor development.
    Hamostaseologie 11/2010; 30 Suppl 1:S150-2. · 1.48 Impact Factor
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    ABSTRACT: Associations of oxytocin receptor gene (OXTR) variants and autism spectrum disorders (ASD) have been reported in earlier studies; in one of the studies associations with IQ and daily living skills were found additionally. Variations of the oxytocin receptor gene might also regulate affect, attachment and separation beyond the diagnostic borders of autism. We tested hypotheses of associations between positive and negative affects and social and emotional loneliness (285 adults), IQ (117 adolescents) and polymorphisms of the oxytocin receptor gene (OXTR rs53576, rs2254298 and rs2228485) in normal subjects. Individuals with the oxytocin OXTR rs53576 A/A genotype showed lower positive affect scores (F=5.532, df=1; p=0.019). This effect was restricted to males (F=13.098, df=1; p=0.00047). Haplotypes constructed with the three markers were associated with positive affect (p=0.0012), negative affect (p<0.0001) and emotional loneliness (p<0.0001). Non-verbal intelligence was significantly reduced in rs53576 A/A adolescents (T=2.247, p=0.027). Our findings support a role for the oxytocin receptor haplotypes in the generation of affectivity, emotional loneliness and IQ.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 04/2009; 33(5):860-6. · 3.55 Impact Factor
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    ABSTRACT: The congenital FVII deficiency (FVIID) is a rare haemorrhagic disorder with an autosomal recessive pattern of inheritance. Data on phenotype and the genotype from 717 subjects in Central Europe (six countries), Latin America (Costa Rica, Venezuela) and United States, enrolled in the Greifswald Registry of FVII Deficiency were analysed. We detected 131 different mutations in 73 homozygous, 145 compound heterozygous and 499 heterozygous subjects. Regional differences were observed in the mutation pattern and the clinical profile of the evaluated patients. Seventy-one per cent of homozygous and 50% of compound heterozygous subjects were symptomatic. The clinical manifestations of the homozygous subjects were characterized by intracranial haemorrhage (2%), gastrointestinal bleeding (17%), haemarthrosis (13%), epistaxis (58%), gum bleeding (38%), easy bruising (37%), haematoma (15%), haematuria (10%) and menorrhagia (19 of 26 females, 73%). The clinical variability and genotype-phenotype correlation was evaluated in the homozygous subjects. The pattern of bleeding symptoms among compound heterozygous patients was severe and similar to that of the homozygous patients. The large-scale analysis of 499 heterozygous subjects shows that 93 (19%) presented with spontaneous bleeding symptoms such as haemarthrosis (4%), epistaxis (54%), gum bleeding (14%), easy bruising (38%), haematoma (23%), haematuria (5%) and menorrhagia (19 of 45 females; 42%). The severe haemorrhages - intracranial and gastrointestinal - were not reported in heterozygous subjects. The clinical variability and the regional differences in the mutation pattern are discussed regarding care and treatment.
    Haemophilia 11/2008; 15(1):267-80. · 3.17 Impact Factor
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    Haematologica 07/2008; 93(8):1273-5. · 5.94 Impact Factor
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    ABSTRACT: The congenital Factor VII deficiency (FVIID) is a rare hemorrhagic disorderwith an autosomal recessive pattern of inheritance and a prevalence of 1:500,000. In 1994 the International Greifswald Registry of congenital FVII deficiency was initiated [1]. We analyzed the phenotype and genotype of subjects,who presented with reduced FVII activities.
    12/2007: pages 247-251;
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    ABSTRACT: The congenital Factor VII deficiency (FVIID) is a rare hemorrhagic disorder with an autosomal recessive pattern of inheritance and a prevalence of 1:500,000. Since 1994 we investigated in the International Greifswald Registry of congenital FVII deficiency more than 900 persons with reduced FVII activity. We analyzed the clinical manifestation with suited questionnaires, and determined the causative F7 genemutation by sequencing of the exons, exon-intron boundaries and the 5’flancing region of the F7 gene.
    12/2007: pages 238-246;
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    ABSTRACT: FVII is a vitamin K-dependent coagulation protease essential for the initiation phase of normal hemostasis. Hereditary FVII deficiency is a rare autosomal recessive bleeding disorder with a variable phenotype. There is a poor correlation between FVII levels, clinical picture and the underlying genetic defect [1, 2]. In the Greifswald FVII deficiency study more than 126 different causative mutations have been characterized by sequence analysis up to now. Among them 67% were missense mutations, 6.3% nonsense mutations, 7% small deletions and 0.7% insertions. 8% of the mutations were located in the 5’ flanking region of the FVII gene and 11% of the mutations affected splice sites [3, 4, 5, 6].
    12/2007: pages 252-255;
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    ABSTRACT: Two families with 'factor X(FX)-Riyadh' have been identified (one of them related to the originally reported family). Affected members of both families exhibit prolongation in prothrombin time (PT) with normal partial thromboplastin time (PTT) and low assay levels of FX, when measured by PT-based assay. They do not have clinical bleeding diathesis, regardless of the PT prolongation. FX genes of the affected family members were analyzed by sequence analysis. A novel missense mutation in exon 4 of the FX gene, which causes the Glu51Lys substitution in the first epidermal growth factor-like domain of FX was found. The Glu51Lys mutation represents a type II mutation with low FX coagulant activity in the extrinsic pathway and normal FX antigen levels. This mutation may result in disruption of the predicted H-bonding between residue Glu51 of FX and the Asn199 residue of the tissue factor (TF) in the FX/TF/factor VIIa ternary complex, producing the phenotype 'FX deficiency Riyadh', with prolonged PT and normal PTT.
    Thrombosis and Haemostasis 05/2007; 97(4):542-5. · 6.09 Impact Factor
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    ABSTRACT: Both reduced postsynaptic dopamine D(2) receptor function and the character variable self-directedness (SDD) are related to the level of alcohol consumption. We examined for interactions between DRD2 exon 8(rs6276), a polymorphism which has been associated with various alcohol-related phenotypes, SDD and alcohol consumption. A total of 144 male and 186 female probands with alcohol dependence or abuse diagnoses and without were included in the study. All subjects were assessed with the alcohol section of the Semi-Structured Assessment for the Genetics of Alcoholism and the Temperament and Character Inventory. Male probands with A/A genotype reported significantly higher alcohol consumption in a typical week (ANOVA; p = 0.024); those with A/A genotype and low SDD showed particularly high consumption levels (interaction DRD2 x SDD: p = 0.019). Alcohol dependence/abuse (DSM-IV) but not nicotine dependence was also relevant for higher alcohol consumption (trend: p = 0.052). In the female group, only alcohol disorders predicted alcohol consumption. Our findings support a role for a gene-personality interaction of DRD2 exon 8 x SDD in alcohol consumption in males.
    Neuropsychobiology 02/2007; 56(1):24-31. · 2.37 Impact Factor
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    ABSTRACT: In this study, eight common polymorphisms associated with venous thrombosis (VT) and thrombophilia factors were analyzed in a Costa Rican case-control study. With the use of polymerase chain reaction (PCR) methods the polymorphisms were detected in 120 patients and 133 controls (mean age <40 years old). It was concluded that a high level of fibrinogen, antiphospholipid antibodies, family history, and the genotype 34LeuLeu of FXIII OR 0.42 (0.20-0.89) showed a significant effect on the risk of VT. Associations between the risk of VT and genetic polymorphisms have been established. Some of these polymorphisms are highly prevalent in Caucasians, but there is a significant geographic variation in their prevalence among different populations. The results of this study support the protective effect of FXIII Val34Leu polymorphism in VT. These findings are consistent with previous reports that included other populations.
    Cell Biochemistry and Function 01/2007; 25(6):739-45. · 1.85 Impact Factor
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    ABSTRACT: We investigated the influence of the factor V haplotype R2 (FVHR2), defined by the mutation FVH1299R, on the thrombin generation in plasma as well as on the clinical expression of bleeding symptoms in patients homozygous for FVIIA294V. Due to its impaired interaction with activated protein C (APC) FVHR2 increases the thrombin generation. Measurements of the endogenous thrombin potential in presence of high APC concentrations showed significant increased ETP values in plasma containing FVHR2 compared to references with factor V wild type. In our measurements this effect is comparable to the increase of thrombin generation caused by FVLeiden. This suggests FVHR2 to be a risk factor for thrombosis similar to factor VLeiden. On the basis of these findings, we investigated the influence of FVHR2 on the clinical expression of bleeding symptoms in factor VII deficient patients. A moderating effect of FVLeiden to bleeding symptoms in hemophilia A and B as well as in case of FIILazio has already been reported by other authors. This effect is explained by the increased APC resistance of FVLeiden. Based on the APC resistance we expected a similar effect for FVHR2. This was confirmed for four patients homozygous for the mutation FVIIA294V. Two of these patients did not carry FVHR2 and show bleeding symptoms. The two asymptomatic patients are heterozygous or homozygous for FVHR2 respectively. This indicates a moderating effect of FVHR2 to bleeding symptoms in patients homozygous for the mutation FVIIA294V.
    12/2006: pages 284-290;
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    ABSTRACT: The molecular basis of a factor VII deficiency was investigated in a Venezuelan patient. The five-year-old boy with a residual FVII:C of 1.7% and FVII:Ag < 8% suffered from epistaxis and easy bruising since birth. By sequence analysis a mutation <60T>C in the 5’ flanking region of the FVII gene and the novel mutation at the IVS7 donor splice site IVS7+1G>A were detected. The mutated splice site is located within the first repeat of a minisatellite region. Each repeat in this region contains a normally silent pseudo splice site. By an electrophoretic mobility shift assay (EMSA) the decrease of the binding of the nuclear factor HNF-4 by the promoter mutation -60T>C could be shown. To characterize the consequence of the mutated splice site IVS7+1G>A we constructed wildtype and mutated minigens spanning exons 7 to 8. HEK 293 cells were transfected with these constructs. In cells transfected with the mutant transcript no normal splicing occurred. Three different cryptic splice sites were used in vitro, all predicting a premature termination.
    12/2006: pages 272-278;
  • R.F. Strey, K. Wulff, W. Schröder, F. H. Herrmann
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    ABSTRACT: In this study we characterized the novel mutations FXG325R, FXE329G and FXG410R by biochemical methods as well as by protein modeling. For the biochemical analysis the proteins have been expressed in HEK 293 cells. The antigen activities (determined using sandwich ELISA) of the mutations FXG325R and FXE329G have been reduced compared to the wild type,whereas FXG410R did not lead to reduced expression. The amidolytic and prothrombinase activities (determined using fluorogenic substrates) of all three mutants have been drastically reduced compared to the wild type. This is in accordance with reduced factor X activities in the (heterozygous) patients. The protein modeling suggests an impaired function of the sodium loop as a result of the mutations FXG325R, FXE329G or FXG410R. Although only Gly410 is located in the sodium loop of factor X, all three mutations lead to a shift of the electrostatic potential in the sodium loop from the acid to the basic range. This could lead to reduced sodium or substrate binding and therefore to an impaired catalytic function of the mutants. Additionally to their influence on the electrostatic potential the mutations FXG325R and FXG410R may lead to steric conflicts as a result of the replacement of the small glycine by the bulky arginine. In the case of FXG325R the side chain of Arg325 inhibits the salt bridge between Ile195 and Asp378, which is important for the formation of the catalytic active conformation of factor Xa. In the mutant FXR410 the side chain of Arg410 may fill the binding site of the sodium ion or of the P1 residue of substrates.
    12/2006: pages 263-271;
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    ABSTRACT: Inherited factor X deficiency (FXD) is a rare (1:1,000,000) recessive bleeding disorder. The clinical and laboratory phenotypes of FXD are poorly correlated and few regional studies on the genotype and the clinical manifestations of FXD are known. To understand the association between clinical manifestations and causative genotype, detailed evaluation of bleeding pattern in a high number of patients is needed. This international study analysed the phenotype and genotype of 102 subjects from Central Europe (Germany, Poland and Slovakia) and Latin America (Costa Rica and Venezuela) with causative mutations in the F10 gene, via sequencing. Twenty-eight homozygous, seven compound-heterozygous and 67 heterozygous FXD subjects were characterized. Twenty-nine different causative mutations, including 15 novel mutations, were analysed. Spontaneous bleeding symptoms in 42 symptomatic individuals (26 homozygous, seven compound heterozygous and nine heterozygous) comprised easy bruising (55%), haematoma (43%), epistaxis (36%), haemarthrosis (33%), intracranial haemorrhage (ICH; 21%), and gastrointestinal (GI) haemorrhage (12%). The manifestation of bleeding symptoms in 9 of 67 (13%) symptomatic heterozygous subjects is described. The bleeding patterns of the enrolled patients showed differences that are associated with the types of F10 mutation, and the corresponding genotypes. The homozygous patients were evaluated for genotype-phenotype correlation. The results suggested that ICH seems to be associated with the F10 mutation Gly380Arg, and possibly with the mutations IVS7-1G>A and Tyr163delAT. A tentative association of other mutations to severe symptoms such as haemarthrosis and GI haemorrhage is reported. The severity of FXD, the genotype-phenotype association, and the results of regional studies are discussed.
    Haemophilia 09/2006; 12(5):479-89. · 3.17 Impact Factor
  • Thrombosis and Haemostasis 05/2006; 95(4):747-8. · 6.09 Impact Factor
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    ABSTRACT: Congenital FVII deficiency is a rare bleeding disorder. Clinical complications are similar to those seen in hemophilia A, and an increased incidence of intracerebral hemorrhage related to birth trauma has been reported. The authors report on an infant who presented at the second day of life with melaena and hematemesis caused by congenital FVII deficiency with minimal activity of 4%. A homozygous mutation IVS4+G-->A, formerly described in 2 siblings, who died of brain hemorrhage within the first month of life, was identified. Severe bleeding events were prevented with prophylactic treatment. Early identification of the underlying mutation helps to assess the risk of hemorrhage and prevent severe bleeding by prophylactic FVII therapy.
    Pediatric Hematology and Oncology 04/2006; 23(2):129-33. · 0.90 Impact Factor
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    ABSTRACT: Twin studies suggest a genetic influence upon perceived parenting. The D(2) dopaminergic receptor is involved in the modulation of social behaviors, and might influence parenting and its perception. A polymorphism (E8) in exon 8 of the D(2) receptor gene (DRD2) has been previously associated with alcoholism-related phenotypes. Similarly, the Pro385Ser variant of GABRA6, the polymorphic gene for GABA(A) receptor alpha6 subunit, has been associated with alcohol- and depression-related traits; and rat pups maintained a more immature GABAR phenotype after brief separation distress. The relationships among DRD2 (E8) and GABRA6 (Pro385Ser) polymorphisms, and perceived parenting were studied here. The association of DRD2 (E8) and GABRA6 (Pro385Ser) genotypes and perceived parental rearing behavior (short-EMBU; questionnaire concerning own memories concerning upbringing) were determined in 207 unrelated adults using multivariate analysis of variance. Temperaments (Temperament and Character Inventory; TCI) were included as covariates. Probands with DRD2 (E8) A/A genotype showed higher scores for father rejection (P = 0.011), parents overprotection (P = 0.021), and father overprotection (P = 0.016) in the total group. An interaction between DRD2 and GABRA6 genotypes on father rejection (P = 0.010) and parents rejection (P = 0.030) was also observed. Further analyses showed that these associations were restricted to the female subgroup only; however, secondary gender-specific analyses were not corrected for multiple testing. Our findings support a role for DRD2 (E8) and GABRA6 (Pro385Ser) in perceived parenting.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 04/2006; 141B(2):167-72. · 3.23 Impact Factor
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    ABSTRACT: Eight common polymorphisms of known myocardial infarction (MI) risk factors (factor V Leiden (FVL), factor V HR2 (FVHR2), factor II 20210G > A (FII), factor VII IVS7 (FVII IVS7), factor VII Arg353Gln (FVII), factor XIII Va134Leu (FXIII), Methylenetetrahydrofolate reductase C677T (MTHFR), Angiotensin Converting Enzyme (ACE)) and environmental risk factors were analyzed in a MI patients of Costa Rica. This case-control study included 186 MI subjects, 95 of them < or = 45 years and 201 age and sex matched controls. With the use of PCR method the polymorphisms were detected and through interviews additional information was collected. Hypercholesterolemia and smoking were associated with a significant risk in younger patients. High fibrinogen level was an important risk factor and interaction with smoking was detected. Mainly, the genotype 34LeuLeu of FXIII showed significant protective effect, (OR 0.32, 95% CI 0.13-0.80) while the other polymorphisms showed no significant difference between the cases and the controls. Carriers of FVII (OR 2.75, 95% CI 1.07-7.02) and FXIII (OR 4.20, 95% CI 2.03-8.67) polymorphisms showed interaction with fibrinogen in the statistical analysis. It was concluded that there was an important interaction between the common risk factors and the polymorphisms (FVII; FXIII) in the development of MI. This is one of the first reports in a Latin-American population dealing with these molecular markers and MI.
    Revista de biologia tropical 03/2006; 54(1):1-11. · 0.55 Impact Factor
  • 01/2006;

Publication Stats

964 Citations
350.60 Total Impact Points

Institutions

  • 2004–2010
    • University of Costa Rica
      • Centro de Investigación en Hematología y Trastornos Afines (CIHATA)
      San José, San José, Costa Rica
  • 2007
    • King Fahad Armed Forces Hospital
      Djidda, Makkah, Saudi Arabia
  • 1985–2007
    • University of Greifswald
      • • Department of Psychiatry and Psychotherapy
      • • Department of Human Genetics
      Greifswald, Mecklenburg-Vorpommern, Germany
  • 2001
    • University of Bonn
      • Institute of Experimental Haematology and Transfusion Medicine (IHT)
      Bonn, North Rhine-Westphalia, Germany
  • 1999–2000
    • Institute of Human Genetics
      Amadavad, Gujarāt, India
  • 1990
    • National Democratic Institute
      Washington, Washington, D.C., United States