bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency of natural rubber latex allergy in adults is increased after multiple operative procedures
Authors: Ruëff F. , Kienitz A. , Schöpf P. , Hugo Hartl W. , Andreβ H. ‐ J. , Zaak D. , Menninger M. , Przybilla B.
Published: March 2003

Background: It has been shown that immediate‐type allergy to natural rubber latex (NRL) affects predominantly health‐care workers and infants with malformations requiring repeated medical procedures. Adult patients with multiple invasive procedures are not thought to be at an increased risk of NRL allergy.

Methods: A total of 325 consecutive adult inpatients (54.4±15.6 years; 219 men, 106 women) awaiting surgical or urologic procedures were assessed by questionnaire‐based history (atopic diseases, number of previous standard operative or endoscopic procedures, intolerance to rubber products, and adverse reactions during medical care), by skin prick tests with different NRL test solutions, by measurement of NRL‐specific IgE in the serum, and, if sensitization to NRL was found, by cutaneous challenge tests with NRL‐containing material. Subjects were classified as sensitized to NRL if skin prick test reactions to NRL were positive or if NRL‐specific IgE antibodies were found. NRL allergy was defined as NRL sensitization and immediate‐type symptoms to NRL.

Results: Thirty‐one of 325 (9.5%) subjects were found to be sensitized to NRL, 14/285 (4.9%) by skin prick testing and 23/323 (7.1%) by NRL‐specific IgE antibodies in the serum. Four individuals (1.2%) were diagnosed as having clinically manifest NRL allergy, and another 27 (8.3%) were sensitized to NRL without symptoms to date. The frequency of previous invasive procedures was zero in eight patients, up to 10 in 245, 11–20 in 52, 21–30 in seven, and over 30 (up to 83) in 13 patients. No association was found between the number of invasive procedures and NRL sensitization without clinical symptoms. However, 3/4 patients with NRL allergy had undergone more than 30 interventions, and 1/4 had had 11 operations. Frequent invasive procedures (more than 10) were significantly associated with NRL allergy (P<0.001). Allergy or sensitization to NRL was associated with atopy (21/31 vs 87/294) (P<0.001).

Conclusions: A remarkable percentage of unselected adult patients undergoing surgical procedures have allergy or sensitization to NRL. Repeated invasive treatment appears to be a risk factor for NRL allergy.
Hidden peanut allergens detected in various foods: findings and legal measures
Authors: Schäppi G. F. , Konrad V. , Imhof D. , Etter R. , Wüthrich B.
Published: March 2003

Background: Undeclared allergens in foodstuffs represent a major health problem for sensitized persons. Until recently, most food control authorities were not in the position to monitor hidden allergens and to take legal measures against their presence in foodstuffs.

Methods: In this study, we employed human sera‐based immunoassay techniques, enabling semiquantitative detection and identification of peanut allergens in a variety of foodstuffs.

Results: This study showed the presence of undeclared allergens in products belonging to various food categories, such as cereals, cookies, cakes, and snacks. The detection limit for peanut contamination was in most instances less than 50 mg peanut material per kg, i.e., less than about 5 mg peanut allergens per kg. We legally objected to products with more than one part per thousand or 1000 mg/kg of peanut contamination.

Conclusions: In most cases, food producers, confronted with our results, were able to detect and eliminate the sources of the contamination. They implemented measures to prevent the presence of hidden peanut allergens in their products, increasing food safety for sensitized persons and overall food quality.
Impaired type‐1 activity and increased NK cells in Gleich's syndrome
Authors: García‐Abujeta J. L. , Martín‐Gil D. , Martín M. , López R. , Suárez A. , Rodríguez F. , Jerez J. , López‐Hoyos M.
Published: March 2003

Background: An altered production of cytokines has been described in Gleich's syndrome. Our aim was to study the cytokine production at the single‐cell level in a patient with Gleich's syndrome and to determine whether it changed during a flare episode.

Methods: Blood samples were obtained from a 30‐year‐old woman diagnosed with Gleich's syndrome before and during the subsequent flare of edema of trunk and arms and weight gain. The major lymphoid subsets (CD4+, CD8+, and CD19+) and natural killer (NK) cells were measured by flow cytometry. Cytokine‐producing T cells (IL‐2, IFN‐γ, and IL‐4) were quantified in whole blood by intracellular staining with specific monoclonal antibodies and flow cytometry analysis after polyclonal stimulation with phorbol 12‐myristate 13‐acetate and ionomycin.

Results: Increased numbers of immature CD4+CD8+ T cells and NK cells were observed in peripheral blood during the asymptomatic period. The latter population significantly decreased during the flare. Type‐1 cells were decreased in both asymptomatic and, more markedly, during the attack with respect to healthy subjects.

Conclusions: The decreased type‐1 response demonstrated in this patient might be the basis of the hypereosinophilia of Gleich's syndrome. Besides, the NK cells might play a role in the pathogenesis of these inflammatory episodes.
Influence of early and current environmental exposure factors on sensitization and outcome of asthma in pre‐school children
Authors: Melén E. , Wickman M. , Nordvall S. , Van Hage‐Hamsten M. , Lindfors A.
Published: March 2003

Background: Exposure to furred pets in early life has been considered to increase the risk of allergic sensitization and consequent development of asthma later in children. However, recently, it has been suggested that early exposure to pets prevents sensitization. The aim of this study was to evaluate the importance of early exposure to pets and other environmental risk factors in asthmatic children.

Methods: This is a follow‐up study after 2 years of a previously investigated group of 193 asthmatic children, aged 1–4 years. The study was completed by 181 children, who were clinically examined; serum IgE antibodies were also measured and a questionnaire was answered.

Results: Children with reported exposure to cats during the first 2 years of life were more likely to have developed sensitization to cat by 4 years of age than unexposed children. High levels of cat allergen (Fel d 1≥8 µg/g dust) were associated with an increased risk of sensitization to cat and, in combination with tobacco smoke, also with the development of more severe asthma.

Conclusions: In young asthmatic children, early exposure to cat and tobacco smoke increased the risk of allergic sensitization and further development of more severe asthma later in childhood.
Exposure to pets and atopy‐related diseases in the first 4 years of life
Authors: Nafstad P. , Magnus P. , Gaarder P. I. , Jaakkola J. J. K.
Published: March 2003

Background: It is still unclear how early‐life exposure to pets is related to children's risk of developing atopy‐related diseases. We estimated associations between early‐life exposure to pets and atopy‐related diseases at 0‐4 years of life in a cohort of Norwegian children.

Methods: A population‐based cohort of 2531 children born in Oslo, Norway, was followed from birth to the age of 4 years. Information on early‐life exposure to pets, a number of possible confounders, and atopy‐related diseases was mainly collected by questionnaire.

Results: In logistic regression analysis adjusting for potential confounders, the odds ratio for being exposed to pets in early life (reference category: not exposed) was, for bronchial obstruction at 0–2 years of life, 1.2 (95% confidence interval 0.9, 1.8); for asthma at the age of 4 years, 0.7 (0.5, 1.1); for allergic rhinitis at the age of 4 years, 0.6 (0.4, 1.0); and for atopic eczema at 0–6 months of life, 0.7 (0.5, 0.9).

Conclusions: The results indicate that early‐life exposure to pets or lifestyle factors associated with exposure to pets reduce the risk of developing atopy‐related diseases in early childhood. However, these findings might also be explained by selection for keeping pets.
Dentist's occupational asthma, rhinoconjunctivitis, and allergic contact dermatitis from methacrylates
Authors: Lindström M. , Alanko K. , Keskinen H. , Kanerva L.
Published: March 2003

Background: Allergic contact dermatitis (ACD) caused by (meth)acrylates (MA) is common in dental personnel. MAs have also caused asthma and rhinoconjunctivitis, but asthma, rhinoconjunctivitis and ACD caused by MAs in the same patient appears to be very rare.

Methods: Occupational asthma and rhinoconjunctivitis were diagnosed in a dentist according to patient history, PEF monitoring, and a work‐simulated bronchial provocation test. ACD was diagnosed by skin‐patch testing with MAs with the occlusive Finn Chamber‐technique.

Results: The patient's skin‐prick test reactions to common environmental allergens and MAs were negative. The total IgE was not elevated. Occupational asthma was diagnosed by a specific inhalation challenge test in which the patient handled liquid dental MAs for 30 min causing a delayed 23% reduction in FEV1. The provocation test also resulted in rhinoconjunctivitis. On patch testing, positive reactions were provoked by several MAs including 2‐hydroxyethyl methacrylate (2‐HEMA) to which the patient was occupationally exposed. The patient has not been able to continue her work with dental MAs.

Conclusions: A case of occupational asthma, rhinoconjunctivitis and ACD caused by dental acrylate compounds is presented. Patients with respiratory hypersensitivity from MAs have to stop working with MAs, whereas patients with ACD from MAs need to avoid direct contact with MAs, but can often continue in their present job if they use no‐touch techniques.
Allergenic cross‐reactivity of Curvularia lunata with other airborne fungal species
Authors: Gupta R. , Singh B. P. , Sridhara S. , Gaur S. N. , Kumar R. , Chaudhary V. K. , Arora N.
Published: March 2003

Background: Curvularia lunata
is an important fungus for respiratory allergic disorders. Previous studies indicated cross‐reactivity of
Curvularia
with other fungi. However, the cross‐reactive allergenic component (s) were not identified. The present work was carried out to study the shared allergenic components of
C. lunata and others.

Methods: Cross‐reactivity studies were performed using pooled hypersensitive patient sera to C. lunata by ELISA, immunoblot, immunoblot inhibition and ELISA inhibition.

Results: Many C. lunata sensitive patients showed positive skin test to five other fungi. Alternaria alternata exhibited maximum (68%) whereas Cladosporium herbarum showed the least (17%) skin reactivity. Immunoblots of fungal extracts with pooled sera showed common proteins. Fusarium solani and C. herbarum showed negligible IgE binding. IgE ELISA inhibition with C. lunata showed 92% inhibition whereas A. alternata and E. nigrum showed 84% and 63%, respectively. Immunoblot inhibition with self protein showed complete loss of IgE‐binding activity. Proteins of 26, 31, 38, 45 and 50 kDa of C. lunata were inhibited by A. alternata and E. nigrum, whereas A. fumigatus inhibited 26, 45 and 50 kDa proteins.

Conclusions: Significant allergenic cross‐reactivity exists among proteins of C. lunata, A. alternata and E. nigrum. Proteins of 26, 31, 38, 45 and 50 kDa are shared allergens in these fungi.
Purification and partial characterization of the major allergen, Cav p 1, from guinea pig Cavia porcellus
Authors: Fahlbusch B. , Rudeschko O. , Szilagyi U. , Schlott B. , Henzgen M. , Schlenvoigt G. , Schubert H.
Published: March 2003

Background: Allergic reaction to guinea pig has been recognized as a problem in domestic settings and work environments for many years. Until recently, limited information was available on the properties of guinea pig allergen(s). In this study the major allergen Cav p 1 was characterized and the N‐terminal amino‐acid sequence was determined.

Methods and results: Sera from 40 patients with IgE‐mediated allergy to guinea pigs were investigated by means of immunoblotting using extracts prepared from guinea pig hair and urine. Three major allergens were identified within both sources with molecular weights (MW) of 8 kDa, 17 kDa and 20 kDa, respectively. From aqueous hair extracts the 20 kDa allergen (Cav p 1) was purified to homogeneity by anion exchange chromatography and reverse‐phase HPLC and the N‐terminal amino‐acid sequence was determined. On the basis of the 15 residues, 57% identity was obtained from computer search with a sub‐sequence of MUP (major urinary protein), a member of the lipocalin superfamily. Allergenic relationships among guinea pig allergens derived from various sources (hair and urine) or different animal species (mouse, rat, cat) were studied by ELISA inhibition assays. Neither urine of mouse, rat and cat, nor hair extracts of rat and cat produced appreciable inhibitions in guinea pig ELISA.

Conclusion Although the physicochemical characteristics of isolated Cav p 1 are very similar to those for other rodent allergens and furthermore partial sequence identity with Mus m 1 was found, it is clearly shown here to be an immunologically independent major allergen.
Validation of a two‐color flow cytometric assay detecting in vitro basophil activation for the diagnosis of IgE‐mediated natural rubber latex allergy
Authors: Ebo D. G. , Lechkar B. , Schuerwegh A. J. , Bridts C. H. , De Clerck L. S. , Stevens W. J.
Published: March 2003

Background:  IgE‐dependent triggering of basophils not only elicits the release of different mediators but also the up‐regulation of certain markers, e.g. CD63, which can be detected by flow cytometry. We intended to investigate if flow cytometric analysis of basophil activation could be a valuable tool in the diagnosis of latex allergy, and to evaluate if the basophil activation test (BAT) could be helpful in determining the clinical significance of a positive latex IgE in individuals with negative history and negative latex skin test. Additionally we aimed to determine the role of cross‐reactive carbohydrate determinants (CCDs) in causing positive latex IgE without apparent clinical significance.

Methods:  Twelve healthy controls without a history of latex hypersensitivity with a negative latex IgE and skin test (group 1), 24 individuals without a history of latex hypersensitivity with a negative latex IgE and skin test but with other inhalant allergies (group 2), and 29 latex allergic patients with a compelling history of latex allergy with a positive latex IgE and prick test (group 3) were enrolled. The diagnostic performances of the BAT were further evaluated in 13 individuals with a history of latex allergy but with negative specific IgE and/or skin test (group 4). Twenty‐four individuals with positive latex IgE without apparent clinical relevance, i.e. without history of latex hypersensitivity and negative latex skin tests, were also analyzed (group 5). The putative role of CCDs causing positive latex IgE results without apparent clinical significance was evaluated by quantification of IgE for bromelain.

Results:  According, to the receiver operating characteristics(ROC)‐generated threshold value of 17% between latex allergic patients and the pooled group of nonlatex allergic individuals, the sensitivity and specificity of the basophil activation test was 93.1% and 91.7%, respectively. In healthy controls, allergic patients without latex hypersensitivity and latex allergic patients the number of positive BATs was 0/12, 3/24 and 27/29, respectively. In the individuals with an evocative history of latex allergy but with negative latex IgE and/or skin test the BAT was positive in all 13 cases. Twenty of 24 individuals without apparent latex allergy but with positive latex IgE had a negative BAT. IgE for bromelain was positive in 1/19 sera from group 2, 1/24 sera from group 3, none of the 8 sera from group 4, but in 16/18 sera from group 5, respectively.

Conclusion:  Flow cytometric analysis of activated basophils seems a highly sensitive and specific tool for diagnosing latex allergy. In addition, the technique might help to determine the clinical relevance of positive IgE quantification in the absence of overt latex allergy. CCDs of natural rubber latex allergens were confirmed to mimic latex sensitization.
Pru p 3 (LTP) content in peach extracts
Authors: Carnés J. , Fernández‐Caldas E. , Gallego M. T. , Ferrer A. , Cuesta‐Herranz J.
Published: March 2003

Background: Lipid transfer proteins are molecules widely distributed in fruits. Sensitization to LTP is frequent in fruit sensitive patients. The aims of this study were to purify LTP and to assess the content of LTP in ripe peach peel and pulp extracts by ELISA inhibition using polyclonal antibodies.

Methods: LTP was purified from ripe yellow peach peel by two different column chromatography methods. A polyclonal antibody was produced by injecting purified LTP into two New Zealand white rabbits. ELISA inhibition and rabbit monospecific polyclonal antibody were used to calculate the LTP content in Springcrest and Miraflores varieties of peach peel and pulp extracts. Purified LTP (2.5 mg/ml) was used to skin test 24 peach‐sensitive patients.

Results: The purified LTP showed a single band at approximately 9 kDa. The polyclonal antibody raised anti LTP recognized only the LTP molecule in the peach extracts. LTP content, expressed in µg/mg of freeze‐dried extract in four extracts were: yellow peach peel, 15.48; yellow peach pulp 2.25; red peach peel 14.67 and red peach pulp 1.84. Twenty patients (83.3%) had a positive skin test with purified LTP.

Conclusions: We have developed a system to determine the concentration of LTP in peach extracts. LTP in peel extracts is approximately seven times greater than in pulp.
Relationship between total and allergen‐specific IgE serum levels and presence of symptoms in farm workers sensitized to Tetranychus urticae
Authors: Gargano D. , Romano C. , Manguso F. , Cutajar M. , Altucci P. , Astarita C.
Published: March 2003

Background: Clinical complaints in atopic subjects with asthma and rhinitis occur more frequently in the presence of high total and allergen‐specific IgE serum levels. Here we report on the relationship between total and allergen‐specific IgE serum levels and presence of symptoms in an unselected farmer population sensitized to Tetranychus urticae (TU).

Methods: Farmers were recruited as previously described. Total IgE and allergen‐specific IgE were measured by immunoassay in TU‐positive skin prick test (SPT) farmers (n = 58) and two control groups including Dermatophagoides pteronyssinus (Dp)‐positive SPT subjects (n = 40) and non‐atopic, TU‐negative SPT healthy farmers (n = 25).

Results: Both TU+ and Dp+ subjects had significantly higher total IgE values (P < 0.001) than healthy non‐atopic subjects. TU‐specific IgE levels were significantly more elevated in symptomatic than non‐symptomatic TU+ subjects (P = 0.028). Dp‐specific IgE levels were higher in symptomatic than non‐symptomatic Dp+ subjects (P = 0.003). Finally, total IgE levels were significantly higher in the symptomatic than non‐symptomatic subgroups in both TU+ and Dp+ subjects (P < 0.0001 and P = 0.007, respectively). Logistic regression analysis showed that only total IgE concentrations were significant predictors of current symptoms in TU+ subjects.

Conclusions: High total IgE and allergen‐specific IgE levels are associated with symptoms in TU+ subjects. Definition of their predictive value requires further studies.
The upper and lower airway responses to nasal challenge with house‐dust mite Blomia tropicalis
Authors: Wang D. Y. , Goh D. Y. T. , Ho A. K. L. , Chew F. T. , Yeoh K. H. , Lee B. W.
Published: March 2003

Background: The house dust mite Blomia tropicalis (B. tropicalis) was found to be the most prevalent domestic mite in Singapore. However, its pathogenicity in allergic airway diseases remains to be investigated.

Methods: Twenty adults with persistent allergic rhinitis (PAR) were studied. Five had a history of asthma, and all were asymptomatic except one who was under treatment with low‐dose inhaled corticosteroid. Nasal challenge was carried out by nasal spray with phosphate‐buffered saline (PBS) and with increasing concentrations of crude B. tropicalis extracts (0.6, 6.0 and 60 µg/ml) at 15 min intervals. Subjective symptom scores and absolute number of sneezes were recorded together with objective measurements of spirometry (forced expiratory volume in 1 s, FEV1) and acoustic rhinomanometry (volume of the nasal cavity). These were performed at baseline, 5 min after each incremental challenge, and 30 min, 1 h, 3 h, 5 h and 7 h after the last challenge. Meanwhile, concentrations of mediators in nasal secretions (tryptase, leukotriene C4 (LTC4) and eosinophil cationic protein (ECP)) were measured in nasal aspirate samples at similar time intervals. An identical (control) challenge procedure with PBS alone was repeated in seven patients after a washout period of at least 2 weeks.

Results: Significant increases in the subjective and objective nasal symptoms, together with a significant increase of tryptase and LTC4 concentrations in nasal secretion, were found 5 min after each challenge with B. tropicalis, but not with PBS. There was no definitive pattern of the late‐phase nasal response in either subjective symptoms or objective measurements. Three patients (3/5) with a history of asthma showed a fall in FEV1 readings (33%, 22% and 11% from baseline, respectively) at 7 h post challenge with concomitant mild wheezing in the night.

Conclusions: Our study demonstrates direct evidence of allergic nasal response to B. tropicalis in sensitized adults. It shows that nasal provocation may also provoke concomitant asthmatic symptoms during the late‐phase reaction, especially in people with a history of asthma.
Limpet anaphylaxis: cross‐reactivity between limpet and house‐dust mite Dermatophagoides pteronyssinus
Authors: Azofra J. , Lombardero M.
Published: March 2003

Background: Limpet is a mollusc that is frequently found along the shores of warm seas. Few allergic reactions to limpet have been described, and cross‐reactivity with house‐dust mites has not been established.

Methods: We report five patients with anaphylactic reactions due to limpet ingestion. A limpet extract was prepared and skin prick tests (SPT), radioallergosorbent assays (RAST), sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS‐PAGE), and IgE‐immunoblotting were performed. In order to evaluate cross‐reactivity, an immunoblotting inhibition assay with Dermatophagoides pteronyssinus was also done.

Results: All patients were asthmatics sensitized to house‐dust mites. In each case, severe bronchospasm was evidenced, and three required mechanical ventilation. Positive SPT with limpet extract was found in the four patients tested. RAST showed specific IgE on each patient's sera. Immunoblotting showed several allergenic fractions with a wide molecular weight range (15–250 kDa). D. pteronyssinus inhibited IgE‐binding molecules above 50 kDa in the limpet extract, particularly one molecule of 75 kDa.

Conclusions: We describe five patients with IgE‐mediated limpet allergy. Severe bronchospasm was the most important symptom. Cross‐reactivity with D. pteronyssinus was demonstrated.
The promise of and problems with evidence‐based medicine for paediatric asthma management
Authors: Smyth R. L. , O'Byrne P. M.
Published: March 2003

The concept of ‘evidence‐based medicine’ has now been in widespread use in clinical practice for over a decade. There are different types of clinical study, which may provide evidence on which to base clinical decisions, but some are much less robust than others. In making decisions about treatment, one of the highest levels of evidence in primary research is the randomized controlled trial. This study design has been used in clinical research for over 50 years. Systematic reviews of randomized controlled trial are scientific studies that review, critically appraise and, where appropriate, aggregate results from a number of different randomized controlled trials. They are increasingly being used throughout health care to provide guidance about treatment. Under the auspices of The Cochrane Collaboration, systematic reviews of randomized controlled trials are being conducted across the whole of health care. One of the most active areas for this work is within the field of asthma and clinicians are now able to access a large number of different systematic reviews on The Cochrane Library. If used appropriately, they can aid the clinician in making decisions about individual patients and provide a sound evidence base from which clinical guidelines can be developed.
Evidence‐based decision making and asthma in the internet age: the tools of the trade
Authors: Jadad A. R.
Published: March 2003

At the dawn of the Information Age, the practice of evidence‐based decision making (EBDM) is still hindered by many important barriers related to the decision makers, to the evidence per se or to the health system. Some of these barriers, particularly those related to the distillation, dissemination and packaging of research evidence, could be overcome by recent and ongoing developments in portable/wearable computers, internet appliances, multimedia and wireless broadband internet traffic. This article describes specific EBDM‐related tools, with emphasis on internet‐enabled “how to” books; and tools to improve the quality of reporting research, to formulate questions; to search for evidence; to access journals, systematic reviews and guidelines; to interact with organizations promoting EBDM; and to tailor evidence to individual cases. However, thinking that all barriers to the practice of EBDM could be solved by fancy information technology is naïve. Barriers related to the generation, interpretation, integration and use of the evidence demand more complex and perhaps unfeasible solutions, as overcoming them will require substantial changes in the structure of the health system, in the politics of science and in the way in which humans think and behave.
Molecular analysis of two pre‐mutations in myotonic dystrophy
Authors: Yamagata Hidehisa , Kinoshita Masanobu , Komori Tetsuo , Kondo Ikuko , Miki Tetsuro
Published: March 2003

Here we report two families with myotonic dystrophy (DM) in which the asymptomatic parent proved to be in a pre‐mutation state. Polymerase chain reaction (PCR) analysis of the region spanning the CTG expansion demonstrated that one father of the proband possessed (CTG)n repeats of n = 12 and 44 copies and the other of 15 and 47. Clinical examination showed no definite signs of DM in these two men. Haplotype analysis of DNA markers close to the DM protein kinase (DMPK) gene suggested a common ancestral DM mutation. A continuous gradient of repeat sizes from normal to abnormal range can explain this phenomenon.
Diversity in expression of glucose‐6‐phosphate dehydrogenase deficiency in females
Authors: Abdulrazzaq Yousef M , Micallef Rosette , Qureshi M Mansoor , Dawodu Adekunle , Ahmed Ibrahim , Khidr Ali , Bastaki Salim Mohamed A , Al‐Khayat Abdulla I , Bayoumi Riad A
Published: March 2003

The aims of this study were to determine the prevalence of glucose‐6‐phosphate dehydrogenase (G6PD) deficiency in the United Arab Emirates (UAE), to describe the different mutations in the population, to determine its prevalence, and to study inheritance patterns in families of G6PD‐deficient individuals. All infants born at Tawam Hospital, Al‐Ain, UAE from January 1994 to September 1996 were screened at birth for their G6PD status. In addition, those attending well‐baby clinics during the period were also screened for the disorder. Families of 40 known G6PD‐deficient individuals, selected randomly from the records of three hospitals in the country, were assessed for G6PD deficiency. Where appropriate, this was followed by definition of G6PD mutations. Of 8198 infants, 746 (9.1%), comprising 15% of males and 5% of females tested, were found to be G6PD deficient. A total of 27 families were further assessed: of these, all but one family had the nt563 Mediterranean mutation. In one family, two individuals had the nt202 African mutation. The high manifestation of G6PD deficiency in women may be due to the preferential expression of the G6PD‐deficient gene and X‐inactivation of the normal gene, and/or to the presence of an ‘enhancer’ gene that makes the expression of the G6PD deficiency more likely. The high level of consanguinity which, theoretically, should result in a high proportion of homozygotes and consequently a higher proportion of females with the deficiency, was not found to be a significant factor.
Tricho‐dento‐osseous syndrome and amelogenesis imperfecta with taurodontism are genetically distinct conditions
Authors: Price JA , Wright JT , Walker SJ , Crawford PJM , Aldred MJ , Hart TC
Published: March 2003

Amelogenesis imperfecta of the hypomaturation‐hypoplasia type with taurodontism (AIHHT) is inherited as a highly penetrant autosomal dominant trait. These dental findings are similar to those of another autosomal dominant condition, the tricho‐dento‐osseous syndrome (TDO), from which AIHHT differs primarily by lack of changes in the hair and bones. TDO is characterized by a highly variable clinical phenotype. While enamel hypoplasia and taurodontism appear to be present in all TDO cases, non‐dental features may be absent, with approximately half of TDO cases losing the kinky/curly hair phenotype seen in infancy by adolescence, and in almost 20% of cases, osseous changes are not evident. The genetic basis for AIHHT is unknown and it has been questioned whether AIHHT and TDO are separate conditions or a spectrum of disease. The genetic basis for TDO has recently been identified as a deletion mutation in the distal‐less 3 (DLX3) transcription factor gene. To determine if AIHHT and TDO represent variable expression of a common DLX3 gene mutation, allelic mutations of the DLX3 gene, or mutations in DLX7 (the linked paralogue to DLX3 on chromosome 17), we have performed mutational analysis and sequencing studies of the DLX3 and DLX7 genes in three individuals (two affected and one unaffected) from a family with AIHHT. Results of the analysis demonstrate that AIHHT and TDO are not due to a common DLX3 gene mutation. Sequence analyses of the DLX3 and DLX7 genes suggest AIHHT is not due to genetic mutations or polymorphisms in the exons of these genes. These results suggest that AIHHT and TDO are two genetically distinct conditions.
Characterisation, phenotypic manifestations and X‐inactivation pattern in 14 patients with X‐autosome translocations
Authors: Kalz‐Füller Burga , Sleegers Eva , Schwanitz Gesa , Schubert Regine
Published: March 2003

Here we describe a group of 14 patients carrying different X‐autosome translocations and exhibiting phenotypes that demonstrate the range of alterations induced by such aberrations.All male carriers of an X‐autosome translocation in our investigation group were infertile, whereas fertility in the female carriers was dependent on the position of the break‐point in the X chromosome. Fertile women with translocation break‐points outside of the critical region (Xq13‐q26) in some cases passed on the translocation to their offspring. In balanced female carriers in our group, the normal X chromosome was usually inactivated, allowing full expression of genes on the translocated segments. In one case, disruption of the dystrophine gene in Xp21 led to the manifestation of Duchenne muscular dystrophy in a female carrier. Inactivation of the derivative X (Xt) in a balanced female carrier led to a partial monosomy of the autosome/disomy of the X chromosome and resulted in an aberrant phenotype. In unbalanced carriers, Xt is generally late‐replicating/inactive, although failed spreading of inactivation to the autosomal segment often results in a partial trisomy, as evidenced by the case of an unbalanced translocation carrier in our group.
The vitamin D receptor FokI start codon polymorphism and bone mineral density in osteoporotic postmenopausal French women
Authors: Lucotte Gérard , Mercier Géraldine , Burckel André
Published: March 2003

This study examined the association between bone mineral density (BMD) and a T/C polymorphism in the first of the two initiation codons in the vitamin D receptor (VDR) gene. The polymorphism was detected using the restriction enzyme FokI, the F allele indicating absence of the first codon and the f allele its presence. The FokI genotype was determined in 124 postmenopausal osteoporotic French women who were 45–90 years old. The distribution of FokI genotypes in the osteoporotics did not differ significantly from that found in a control group. There were no significant differences by FokI genotype groups in our total sample of osteoporotic women for age, years since menopause, height, weight, and BMD at lumbar spine and femoral neck. However, when only those patients under the age of 75 years are analysed (98 subjects), those with the ff genotype (10% of the population) had a significantly lower BMD at the femoral neck than FF and Ff subjects. This suggests that the ff genotype of the VDR gene correlates with decreased BMD at the femoral neck in French postmenopausal women.
Holoprosencephaly, sacral anomalies, and situs ambiguus in an infant with partial monosomy 7q/trisomy 2p and SHH and HLXB9 haploinsufficiency
Authors: Nowaczyk Małgorzata Jm , Huggins Marlene J , Tomkins Darrell J , Rossi Elena , Ramsay Jennifer A , Woulfe John , Scherer Stephen W , Belloni Elena
Published: March 2003

We report an infant with holoprosencephaly (HPE), sacral anomalies, and situs ambiguus with a 46,XY,der(7)t(2;7)(p23.2;q36.1) karyotype as a result of an adjacent‐1 segregation of a t(2;7)pat. The chromosomal abnormality was diagnosed prenatally after sonographic detection of HPE in the fetus. The baby was born at 37 weeks gestation, and died in the newborn period; he had dysmorphic features consistent with HPE sequence. Postmortem internal evaluation showed semilobar HPE, abdominal situs ambiguus, multiple segments of bowel atresia, dilatation of the ureters, and bony sacral anomalies. Molecular analysis confirmed hemizygosity for the SHH and HLXB9 genes, which are likely to be responsible for the HPE and sacral phenotypes, respectively. Immunohistochemical studies showed intact dopaminergic pathways in the mesencephalon, suggesting that midbrain dopamine neuron induction appears to require only one functioning SHH allele.
Atypical movement disorders in the early stages of Huntington's disease: clinical and genetic analysis
Authors: Squitieri Ferdinando , Berardelli Alfredo , Nargi Eleonora , Castellotti Barbara , Mariotti Caterina , Cannella Milena , Luisa Lavitrano Maria , De Grazia Ugo , Gellera Cinzia , Ruggieri Stefano
Published: March 2003

Huntington's disease (HD) is notably difficult to diagnose in the early stages. One reason is that the early clinical manifestations of HD vary widely and sometimes have an atypical onset. In this paper we primarily sought information on affected patients who initially presented with movement disorders other than chorea. We also investigated atypical motor presentations in relation to triplet CAG expansions. After reviewing the clinical records of two neurological centres, we identified patients with a final, documented diagnosis of HD and selected for study 205 patients according to their onset of motor manifestations. CAG repeats were analysed. Of the 205 patients studied, 15 had atypical motor symptoms at onset. In this group we identified three types of initial clinical manifestations other than chorea: parkinsonism, ataxia and dystonia. We conclude that HD patients may have different motor manifestations at the initiation of the illness. Patients with atypical movement disorders in the early stages have larger CAG expansions and an earlier age at onset than HD patients with typical onset chorea.
Familial Prader‐Willi syndrome: case report and a literature review
Authors: McEntagart ME , Webb T , Hardy C , King MD
Published: March 2003

Prader‐Willi syndrome (PWS) is a neurobehavioural disorder arising through a number of different genetic mechanisms. All involve loss of paternal gene expression from chromosome 15q11q13. Although the majority of cases of PWS are sporadic, precise elucidation of the causative genetic mechanism is essential for accurate genetic counselling as the recurrence risk varies according to the mechanism involved. A pair of siblings affected by PWS is described. Neither demonstrates a microscopically visible deletion in 15q11q13 or maternal disomy. Methylation studies at D15S63 and at the SNRPN locus confirm the diagnosis of PWS. Molecular studies reveal biparental inheritance in both siblings with the exception of D15S128 and D15S63 where no paternal contribution is present indicating a deletion of the imprinting centre. Family studies indicate that the father of the siblings carries the deletion which, he has inherited from his mother. The recurrence risk for PWS in his offspring is 50%.
Pedigree parables
Authors: Bennett RL
Published: March 2003

Pedigrees are a foundation of genetic counseling and human genetic research. To protect patient/subject and family privacy and confidentiality it is not unusual to find published pedigrees that have been masked (i.e. a pedigree that has been changed in ways that are obvious to the reader such as diamonds to mask gender) or altered (i.e. changing pedigree information in ways that are not obvious to the reader such as changing gender and birth order or deleting unaffected siblings from the pedigree). Failure to report pedigree data (e.g. omitting ages, ethnicity, etc.) is another measure used to protect subject and family confidentiality. At what point do such practices hinder the recognition of genetic processes? Is there evidence that harm has occurred to subjects who have appeared in published pedigrees? How does the researcher or clinician determine which information is essential to record on the pedigree? The author uses a historical perspective and case examples to illustrate the issues of balancing protection of the genetic subject's privacy with the reporting of unaltered family data. The author presents several critical questions for peer reviewers and investigators to consider when a pedigree is included in a manuscript, or for researchers involved in family studies.
Collagens: building blocks at the end of the development line
Authors: Byers PH
Published: March 2003

Collagens are some of the majr building blocks of the vertebrate body. In addition to their structural role,they are important for cell guidance during development and for maintaining tissue integrity. In their absence, phenotypes range from lethal to mild. These studies demonstrated that collaens,in their rich array, play important roles in development and are significant elements in reading the developmental code.
Ectodermal dysplasias: not only ‘skin’ deep
Authors: Priolo M , Silengo M , Lerone M , Ravazzolo R
Published: March 2003

The ectodermal dysplasias (EDs) are a large and complex nosologic group of diseases; more than 170 different pathologic clinical conditions have been identified. Despite the great number of EDs described so far, few causative genes have been identified. We review EDs in the light of the most recent molecular findings and propose a new classification of EDs integrating both molecular‐genetic data and corresponding clinical findings of related diseases.
The ‘flap’ endonuclease gene FEN1 is excluded as a candidate gene implicated in the CAG repeat expansion underlying Huntington disease
Authors: Otto CJ , Almqvist E , Hayden Mr , Andrew SE
Published: March 2003

At least 12 disorders including Huntington disease (HD) are associated with expansion of a trinucleotide repeat (TNR). Factors contributing to the risk of expansion of TNRs and the mechanism of expansion have not been elucidated. Data from Saccharomyces cerevisiae suggest that the flap endonuclease FEN1 plays a role in expansion of repetitive DNA tracts. It has been hypothesized that insufficiency of FEN1 or a mutant FEN1 might contribute to the occurrence of expansion events of long repetitive DNA tracts after polymerase slippage events during lagging strand synthesis. The expression pattern of FEN1 was determined, and ubiquitous tissue expression, including germ cells, suggested that FEN1 has the potential to be involved in HD. Fifteen HD parent/child pairs that demonstrated intergenerational increases in CAG length of greater than 10 repeats were examined for possible mutations or polymorphisms within the FEN1 gene that could underlie the saltatory repeat expansions seen in these individuals. No alterations were observed compared to 50 controls, excluding FEN1 as a trans‐acting factor underlying TNR expansion. The identification of a candidate gene(s) in HD or other CAG‐expansion disorders implicated in TNR instability will elucidate the mechanism of expansion for this growing family of neurological disorders.
Clinical and molecular studies of a large family with desmin‐associated restrictive cardiomyopathy
Authors: Zhang J , Kumar A , Stalker Hj , Virdi G , Ferrans Vj , Horiba K , Fricker Fj , Wallace Mr
Published: March 2003

Patients with restrictive cardiomyopathy (RC) have impaired diastolic function, but intact systolic function until later stages of the disease, ultimately leading to heart failure. Primary RC is often sporadic, but also may be inherited in an autosomal dominant fashion, particularly the idiopathic forms. Recently there has been great interest in inherited cardiomyopathy associated with myocyte desmin deposition (‘desminopathies’). In some such families, desmin or alpha‐B crystallin gene mutation is the underlying cause, and the desmin accumulation affects skeletal muscle as well, usually causing skeletal myopathy. We describe a large family with apparent autosomal dominant inheritance of desmin‐associated RC spanning four generations, with the age of onset and severity/rate of progression being highly variable. This family is relatively unique in that there is no symptom‐based evidence of skeletal muscle involvement, and the known desminopathy and cardiomyopathy genes/loci have been ruled out. These data support literature suggesting that desmin deposition may be associated with different underlying gene defects, and that a novel desminopathy gene is responsible for the condition in this family.
Identification of fifteen novel mutations and genotype–phenotype relationship in Fabry disease
Authors: Altarescu GM , Goldfarb LG , Park K‐Y , Kaneski C , Jeffries N , Litvak S , Nagle JW , Schiffmann R
Published: March 2003

Fabry disease is an X‐linked recessive disorder caused by a deficiency in the lysosomal enzyme α‐galactosidase A, which results in a progressive multisystem disease. Most families have private mutations and no general correlation between genotype and disease manifestations has been described to date.  Forty‐nine patients (47 males and 2 females) from 36 affected families were selected for the study. Their evaluation included clinical examination, identification of α‐galactosidase A gene mutations and residual enzymatic activity. For mutation detection, each exon with flanking intronic sequences was amplified by polymerase chain reaction (PCR) from the patient's genomic DNA and sequenced. Analysis of the resulting sequences was conducted to identify structural defects in the gene.  Each of the Fabry patients carried a mutation in the α‐galactosidase A gene. Fifteen mutations were novel. They included missense mutations (M51K, Y123M, G261D), nonsense point mutations (E251X) and small insertions or deletions creating a premature translational termination signal (P6X, D93X, W162X, K240X, H302X, I303X, L403X, S345X, G375X, F396X). Residual α‐galactosidase A activity was significantly lower in patients with neuropathic pain (p=0.01) and in patients with mutations leading to a nonconservative amino acid change (p=0.04).  Our findings emphasize the wide variety of genetic mechanisms leading to Fabry disease. A significant genotype–phenotype relationship was found.
Hemochromatosis mutations C282Y and H63D in ‘cis’ phase
Authors: Best LG , Harris PE , Spriggs EL
Published: March 2003

Homozygosity for the C282Y mutation of the HFE gene is a highly significant risk factor for the development of hereditary hemochromatosis (HH) and the majority of patients with HH have this genotype. An Irish/Belgian female with an elevated serum ferritin level and a family history of hemochromatosis was tested for the presence of the C282Y and H63D mutations. Results of digested PCR products have shown the patient to be homozygous for C282Y mutation and heterozygous for H63D mutation. Sequencing confirmed these findings. Genotyping of the patient's offspring and husband has also indicated the inheritance of both C282Y and H63D in ‘cis’. Implications of this finding are: 1) the compound heterozygous state is by far the most common, but not the universal, phase for individuals found to be heterozygous for the two mutations, C282Y and H63D; 2) the C282Y and H63D mutations in the ‘cis’ phase may account for some cases of questionable parentage.
PAX6 mutation in a family with aniridia, congenital ptosis, and mental retardation
Authors: Malandrini A , Mari F , Palmeri S , Gambelli S , Berti G , Bruttini M , Bardelli AM , Williamson K , Van Heyningen V , Renieri A
Published: March 2003

Congenital aniridia is due to deletions and point mutations in the PAX6 gene. We describe here a case of a mother and her two sons with a syndrome comprising congenital aniridia, ptosis, and slight mental retardation. The sons also show behavioral changes. The possibility of deletion around the PAX6 locus was excluded by polymorphism studies and fluorescence in situ hybridization analysis. Mutation screening of the PAX6 gene revealed the presence of a transversion C719A, resulting in the substitution of arginine for serine at residue 119. We suggest that this missense mutation is responsible both for aniridia and ptosis, and possibly also for the observed cognitive dysfunction in this family.
Medical genetics and patient use of the Internet
Authors: Christian SM , Kieffer SA , Leonard NJ
Published: March 2003

Clinical experience suggests that the Internet is increasingly becoming a resource for patients seen in medical genetics. A prospective analysis was performed exploring patient use of the Internet prior to attending a medical genetics appointment. We administered 200 questionnaires assessing: 1) the frequency of patient use of the Internet for genetic information, 2) factors associated with Internet use, 3) patient assessment of the value of the information, and 4) patient views of the responsibility of medical genetics professionals to be familiar with Internet information. Results show that 77% (153/200) of patients have access to the Internet of which 29% (44/153) report searching the Internet for genetic information. A correlation was found between patient use of the Internet and reason for referral (p<0.001), presence of a specific diagnosis (p<0.001), and frequency of Internet use (p<0.05). Overall, 80% (33/41) of patients found Internet information useful. Seventy‐four percent (115/155) believed that medical genetics professionals have a responsibility to review relevant Internet sites for accuracy and 80% (123/153) felt that professionals should provide their patients with appropriate and useful Internet sites. These results suggest that the role of medical genetics professionals is changing as a result of the development of the Internet.