Diagnosis of primary immunodeficiency diseases in pediatric patients hospitalized for recurrent, severe, or unusual infections

Background: Primary immunodeficiency diseases (PID) usually presents itself with recurrent, severe, and unusual infections, along with autoimmunity and various other malignancies. But, the diversity of PID often makes the diagnosis of patients difficult for physicians other than clinical immunologists. This study aimed to describe the characteristics of patients diagnosed with PIDs during the inpatient treatment for infectious diseases, and to highlight the cases in which a PID diagnosis should be considered.Methods: The clinical, immunological, and molecular features of 81 pediatric patients treated for infectious diseases, who were diagnosed with a PID during hospitalization was retrospec-tively analyzed. The diagnosis was based on the PID criteria of the International Union of Immunological Societies.Results: The five main PID sub-types were identified. Predominantly, antibody deficiencies were the most common (61.7%) group. The average delay in diagnosis was 34.6 months, and the positive family history rate was 24.7%, while the consanguineous marriage rate was 45.7%. Around thirty-five (43%) patients were found to have mutated PID-related genes. While lower respiratory tract infections were the most common symptom, a fever of unknown origin was another remarkable diagnosis. Eight (9.9%) patients underwent allogeneic hematopoietic stem cell transplantation.Conclusions: Clinicians should consider a PID diagnosis, especially in the cases of recurrent, severe, or atypical infections. Increased knowledge of the alarm features of PID can promote early diagnosis (AU)

Clinical and immunological features of 44 common variable immunodeficiency patients: the experience of a single center in Turkey

INTRODUCTION AND OBJECTIVES: Common variable immunodeficiency (CVID) is one of the most prevalent forms of primary immunodeficiency characterized by hypogammaglobinemia. Its heterogeneous clinical features include recurrent respiratory tract infections and other complications such as gastrointestinal, autoimmunity, and lymphoproliferative disorders. The aim of this article is to evaluate the general characteristics of CVID patients. MATERIALS AND METHODS: Clinical and immunological features of 44 CVID patients were evaluated retrospectively with long-term follow-up. Patients who participated in the study were diagnosed according to the criteria of the European Society for Immunodeficiency Diseases (ESID). RESULTS: The median age at onset of symptoms was 2.75 years (range 6 months to 17 years), and the median age at diagnosis was 7.75 years (range 4-20 years). The average delay in diagnosis was 4.6 years (range 1-14 years). Positive family history was 18.2%. Before treatment, patients' median total serum IgG was 271.5mg/dL, median IgA was 7.5mg/dL, and median IgM was 21mg/dL. Infections were the most common clinical manifestation, and 63.6% of patients presented with sinopulmonary infection as the first manifestation. Bronchiectasis developed in 23 CVID subjects, while bronchiectasis was detected prior to CVID diagnosis in eight patients. All patients received immunoglobulin replacement therapy, and one patient died because of granulomatous lymphocytic interstitial lung disease (GLILD). CONCLUSIONS: CVID is a heterogeneous group of immunologic disorders with unknown etiology. There are significant differences in the clinical presentation and prevalence of CVID-related complications among countries. Local guidelines for diagnosis and clinical follow-up are needed

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Clinical and immunological features of 44 common variable immunodeficiency patients: the experience of a single center in Turkey.

INTRODUCTION AND OBJECTIVES: Common variable immunodeficiency (CVID) is one of the most prevalent forms of primary immunodeficiency characterized by hypogammaglobinemia. Its heterogeneous clinical features include recurrent respiratory tract infections and other complications such as gastrointestinal, autoimmunity, and lymphoproliferative disorders. The aim of this article is to evaluate the general characteristics of CVID patients. MATERIALS AND METHODS: Clinical and immunological features of 44 CVID patients were evaluated retrospectively with long-term follow-up. Patients who participated in the study were diagnosed according to the criteria of the European Society for Immunodeficiency Diseases (ESID). RESULTS: The median age at onset of symptoms was 2.75 years (range 6 months to 17 years), and the median age at diagnosis was 7.75 years (range 4-20 years). The average delay in diagnosis was 4.6 years (range 1-14 years). Positive family history was 18.2%. Before treatment, patients' median total serum IgG was 271.5mg/dL, median IgA was 7.5mg/dL, and median IgM was 21mg/dL. Infections were the most common clinical manifestation, and 63.6% of patients presented with sinopulmonary infection as the first manifestation. Bronchiectasis developed in 23 CVID subjects, while bronchiectasis was detected prior to CVID diagnosis in eight patients. All patients received immunoglobulin replacement therapy, and one patient died because of granulomatous lymphocytic interstitial lung disease (GLILD). CONCLUSIONS: CVID is a heterogeneous group of immunologic disorders with unknown etiology. There are significant differences in the clinical presentation and prevalence of CVID-related complications among countries. Local guidelines for diagnosis and clinical follow-up are needed.

Factors affecting physicians' perception of the overuse of antibiotics.

OBJECTIVE: We aimed to determine the reasons for irrational antibiotic use, to evaluate knowledge, attitudes, and behaviors of physicians regarding such use, to find factors affecting knowledge of physicians, and to explore precautions that need to be taken to stop irrational antibiotic use. MATERIAL AND METHODS: We performed the study between January 2014 and June 2014. We included 202 physicians who answered a questionnaire with 22 multiple-choice questions about knowledge (eight questions), behavior and attitudes of physicians (nine questions), and recommendations for reducing antibiotic consumption (five questions). Answers to all questions were assessed according to the physician's age, educational status, metropolitan areas, and healthcare facilities. RESULTS: The effects of parents' expectations and satisfaction (7.4%-40.0%) (P<0.0001) and socioeconomical status of families (33%-62%) (P=0.007) increased as the participants' age decreased. Participants working at public hospitals (42.6%) considered expectations and satisfaction of parents more important than other participants (10.5%-26.9%; P=0.002). Rapid recovery of patients was not an essential determinant for administering antibiotics for pediatricians (25.7%) and pediatric assistants (26.9%). However, it was important for emergency physicians (55.6%) and family physicians (60%, P=0.016). Physicians working at university hospitals did not consider this determinant as important as physicians working in other healthcare facilities (P=0.001). CONCLUSION: To determine the obstacles associated with promoting rational antibiotic usage, every country should assess the attitudes, behavior, and knowledge of physicians related to such use. The present study is one of the few in Turkey to address the problems associated with irrational antibiotic use.

Inappropriate antimicrobial use in Turkish pediatric hospitals: a multicenter point prevalence survey.

OBJECTIVES: Although well-defined principles of rational antimicrobial use are available, inappropriate prescribing patterns are reported worldwide. Accurate information on the usage of antimicrobials, including factors associated with and influencing their use, is valuable for improving the quality of prescription practices. METHODS: In this cross-sectional point prevalence survey, data on patients hospitalized in 12 different children's hospitals were collected on a single day. Appropriateness of prescription was compared between the types of antimicrobials prescribed, indications, wards, and presence of/consultation with an infectious disease physician (IDP). RESULTS: A total 711 of 1302 (54.6%) patients evaluated were receiving one or more antimicrobial drugs. The antimicrobial prescription rate was highest in pediatric intensive care (75.7%) and lowest in the surgery wards (37.0%). Of the 711 patients receiving antimicrobials, 332 patients (46.7%) were found to be receiving at least one inappropriately prescribed drug. Inappropriate use was most frequent in surgery wards (80.2%), while it was less common in oncology wards (31.8%; p<0.001). Respiratory tract infection was the most common indication for antimicrobial use (29.4%). Inappropriate use was more common in deep-seated infections (54.7%) and respiratory infections (56.5%). Fluoroquinolones were used inappropriately more than any other drugs (81.8%, p=0.021). Consultation with an IDP appears to increase appropriate antimicrobial use (p=0.008). CONCLUSIONS: Inappropriate antimicrobial use remains a common problem in Turkish pediatric hospitals. Consultation with an IDP and prescribing antimicrobial drugs according to microbiological test results could decrease the inappropriate use of antimicrobials.

Skin test hypersensitivity for childhood asthma in Istanbul during a period of 16 years.

BACKGROUND: For diagnosis of allergic disorders, besides history and physical examination, many in vivo and in vitro laboratory tests are used. Skin prick test (SPT) is an easily performed and valuable test in children. Our aim was to evaluate the SPT results of asthmatic children according to age and gender, in Istanbul and its neighborhood, followed for a period of 16 years. MATERIAL AND METHODS: Consecutive 5080 asthmatic children, aged 1 to 18 years, admitted to Pediatric Allergy Policlinics of Istanbul University Cerrahpasa Medicine Faculty from 1987 to 2003, were screened retrospectively for 10 frequently exposed allergens. RESULTS: 3086 cases (61 %) had SPT reactivity for one and/or for multiple allergens; the SPT reactivity percentages of the exposed allergens was 50 % (2554 cases) for house dust mites DP, 49 % (2462 cases) for house dust mites DF, 15 % (784 cases) for cat dander, 10 % (525 cases) for dog dander, 4 % (228 cases) for lamb wool, 10 % (504 cases) for wheat, 3 % (162 cases) for egg white, 6 % (345 cases) for hazelnut pollen, 6 % (318 cases) for Candida Albicans, 6 % (326 cases) for Aspergillus Fumigatus. CONCLUSION: While house dust mites were determined as the predominant allergen for each age groups in this study, allergy against cat dander was the third important allergen in sequence, as cat is a domestic pet which is frequently kept at home in Turkey.

Skin test hypersensitivity for childhood asthma in Istanbul during a period of 16 years

Background: For diagnosis of allergic disorders, besides history and physical examination, many in vivo and in vitro laboratory tests are used. Skin prick test (SPT) is an easily performed and valuable test in children. Our aim was to evaluate the SPT results of asthmatic children according to age and gender, in Istanbul and its neighborhood, followed for a period of 16 years. Material and methods: Consecutive 5080 asthmatic children, aged 1 to 18 years, admitted to Pediatric Allergy Policlinics of Istanbul University Cerrahpasa Medicine Faculty from 1987 to 2003, were screened retrospectively for 10 frequently exposed allergens. Results: 3086 cases (61 %) had SPT reactivity for one and/or for multiple allergens; the SPT reactivity percentages of the exposed allergens was 50% (2554 cases) for house dust mites DP, 49% (2462 cases) for house dust mites DF, 15% (784 cases) for cat dander, 10 % (525 cases) for dog dander, 4% (228 cases) for lamb wool, 10% (504 cases) for wheat, 3% (162 cases) for egg white, 6% (345 cases) for hazelnut pollen, 6% (318 cases) for Candida Albicans, 6% (326 cases) for Aspergillus Fumigatus. Conclusion: While house dust mites were determined as the predominant allergen for each age groups in this study, allergy against cat dander was the third important allergen in sequence, as cat is a domestic pet which is frequently kept at home in Turkey

Antecedentes: Para el diagnóstico de los trastornos alérgicos, además de la exploración física y de la historia clínica se emplean muchas pruebas de laboratorio in vivo e in vitro. La prueba por punción cutánea (prick test) (PC) es una prueba fácil de realizar y valiosa en niños. Nuestro objetivo era evaluar los resultados de las PC en niños asmáticos de Estambul y su periferia según su edad y sexo, con un seguimiento de 16 años. Material y métodos: Se efectuó un estudio retrospectivo mediante PC con 10 alergenos de exposición frecuente a 5.080 niños asmáticos, de 1 a 18 años de edad, consecutivamente tratados en la Policlínica de Alergología Pediátrica de la Facultad de Medicina Cerrahpasa de la Universidad de Estambul entre 1987 y 2003. Resultados: 3.086 casos (el 61%) mostraron reactividad a la PC con uno o más alergenos; los porcentajes de reactividad a la PC con los alergenos frecuentes fueron: el 50% (2.554 casos) para los ácaros del polvo doméstico de la especie D.p., el 49% (2.462 casos) para los ácaros del polvo doméstico de la especie D.f., el 15% (784 casos) para epitelio de gato, el 10% (525 casos) para epitelio de perro, el 4% (228 casos) para la lana de cordero, el 10% (504 casos) para el trigo, el 3% (162 casos) para la clara de huevo, el 6% (345 casos) para el polen de avellano, el 6% (318 casos) para la Candida albicans, y el 6% (326 casos) para el Aspergillus fumigatus. Conclusión: Aunque los ácaros del polvo domésticos se establecieron como el alergeno predominante en todos los grupos de edad del estudio, la alergia a epitelio de gato fue el tercer alergeno en importancia, ya que el gato es un animal doméstico presente en muchos hogares turcos

Psychological problems in Turkish asthmatic children and their families.

BACKGROUND: Asthma is a chronic respiratory disorder characterized by recurrent episodes of impaired breathing. The disease causes psychological problems due to hospitalization, long-term medication use, and restricted social life. OBJECTIVE: The aim of this study was to investigate the relationship between the severity and duration of asthma and psychological problems in asthmatic children, as well as the probability of maternal anxiety. METHODS: Thirty-seven children with mild asthma, 55 with moderate asthma and eight with severe asthma were compared with 50 healthy children. The severity of asthma was evaluated using the Pearlman-Bierman classification. Psychological adjustment was measured using the Achenback child Behavior checklist and Spielberger's scale. RESULTS: Emotional factors and family dynamics were found to be triggering factors for disease attacks in 16% of children with mild asthma, 38% of those with moderate asthma and 63% of those with severe asthma (p < 0.05). There was no significant difference in the mean maternal anxiety score between the disease severity groups (p > 0.05). The mean depression score was significantly higher in children with moderate and severe asthma than in those with mild asthma (p < 0.05). Disease duration showed no effect on depression and anxiety. CONCLUSION: Both asthmatic children and their mothers are negatively affected by the disease.

Psychological problems in turkish asthmatic children and their families

Background: Asthma is a chronic respiratory disorder characterized by recurrent episodes of impaired breathing. The disease causes psychological problems due to hospitalization, long-term medication use, and restricted social life. Objective: The aim of this study was to investigate the relationship between the severity and duration of asthma and psychological problems in asthmatic children, as well as the probability of maternal anxiety. Methods: Thirty-seven children with mild asthma, 55 with moderate asthma and eight with severe asthma were compered with 50 healthy children. The severity of asthma was evaluated using the Pearlman-Bierman classification. Psychological adjustment was measured using the Achenback child Behavior checklist and Spielberger's scale. Results: Emotional factors and family dynamics were found to be triggering factors for disease attacks in 16 % of children with mild asthma, 38 % of those with moderate asthma and 63 % of those with severe asthma (p < 0.05). There was no significant difference in the mean maternal anxiety score between the disease severity groups (p > 0.05). The mean depression score was significantly higher in children with moderate and severe asthma than in those with mild asthma (p < 0.05). Disease duration showed no effect on depression and anxiety. Conclusion: Both asthmatic children and their mothers are negatively affected by the disease (AU)

Antecedentes: El asma es un trastorno respiratorio crónico caracterizado por episodios recurrentes de dificultad para respirar. La enfermedad causa algunos problemas psicológicos por la necesidad de hospitalización, el uso de medicación a largo plazo y la limitación de la vida social. Objetivo: El objetivo de este estudio era investigar la relación entre la gravedad y la duración del asma y los problemas psicológicos en niños asmáticos y la probabilidad de ansiedad de las madres. Métodos: Se comparó a 37 niños con asma leve, 55 con asma moderada y 8 con asma grave con 50 niños sanos. La gravedad del asma se evaluó utilizando la clasificación de Pearlman-Bierman. La adaptación psicológica se midió empleando la lista de comprobación de comportamiento infantil de Achenback y la escala de Spielberger. Resultados: Se comprobó que los factores emocionales y la dinámica familiar eran factores desencadenantes de las crisis de asma en el 16 por ciento de los pacientes con asma leve, el 38 por ciento de los enfermos con asma moderada y el 63 por ciento de los pacientes con asma grave (p 0,05).En los grupos con asma moderada y grave se observó que la puntuación media de depresión era significativamente mayor que en el grupo con asma leve (p < 0,05). Se apreció que la duración de la enfermedad no influía en la depresión y la ansiedad. Conclusión: La enfermedad afecta negativamente a los niños asmáticos y a las madres (AU)

Cystic fibrosis mutations and associated haplotypes in Turkish cystic fibrosis patients.

Identification of mutations causing cystic fibrosis (CF) in the Turkish population is essential for assessment of the molecular basis of CF in Turkey and the development of strategies for prenatal diagnosis and genetic counseling. Here, we present an updated report of mutations found in the Turkish CF population from an extensive screening study of the entire coding region, including exon-intron boundaries and the promoter region. Cases for which mutations could not be identified were also screened for previously defined large alterations and (TG)mTn-M470V loci. This study revealed a total of 27 different mutations accounting for almost 60% of disease genes in the Turkish population. In this study, we also identified the haplotypes associated with 17 mutations and those associated with unknown mutations. The mutation spectrum of CF in Turkey and its associated haplotypes indicated the presence of a major Mediterranean component in the contemporary Turkish population.

Ultrastructural examination of bronchial biopsy specimens from children with moderate asthma.

BACKGROUND: Few studies have evaluated the asthmatic airway in childhood. The aim of this study was to assess the histopathological changes occurring in the bronchi of children with moderate asthma using light and electron microscopy. METHODS: Bronchial biopsy specimens from 10 children with moderate asthma (seven boys) of mean (SD) age 9.3 (3.8) years (range 5-14) were examined by light and electron microscopy. Patients had not had a respiratory infection for at least one month and they had not been treated with steroids or sodium cromoglycate for four weeks before the study. Bronchoscopy was performed under general anaesthesia using a Karl Storz rigid paediatric bronchoscope. Biopsy materials were stained with uracyl acetate and lead citrate and evaluated under a Zeiss-10 electron microscope and light microscope. RESULTS: The most important finding was thickening and hyalinization of the basement membrane in nine patients. The ciliated epithelial cells showed loss of cilia in some cases. Overactive fibroblasts were consistently found. Six patients had degranulating mast cells and lymphocyte infiltration in the submucosa. Eosinophils were seen in only one biopsy sample. CONCLUSION: Children with moderate asthma develop bronchial inflammation similar to the reaction observed in adults. However, in our study the inflammation was rich in lymphocytes rather than eosinophils.

Haemophilus influenzae type b colonization in children in a hospital-based day care center.

We sought to assess the effect of day care center (DCC) attendance and parental health care work environment on the prevalence of Haemophilus influenzae type b (Hib) pharyngeal colonization in children in Turkey. Children of health care workers were evaluated by nasopharyngeal culture specimens obtained prior to enrollment at a hospital-based DCC at Cerrahpasa Medical Faculty (CMF-DCC) and then again after 3 months of attendance. A larger cohort from this same DCC was evaluated after 6 months of attendance and compared to a group of children of non-health care workers enrolled in Bahcelievler-DCC. As is standard of care in Turkey, none of these children had received the Hib vaccine. Fifty children of health care workers were evaluated prior to their enrollment and then again after 3 months at CMF-DCC. The incidence of Hib carrier state at enrollment was 4% and increased to 22% after 3 months at the DCC. To assess the affect of parental health care employment on Hib carriage rates, 103 children from CMF-DCC and 40 children of non-medical families at Bahcelievler-DCC were evaluated. Hib carrier state was identified in 40.7 and 47.5% after more than 6 months of attendance at CMF-DCC and Bahcelievler-DCC, respectively. No significant difference was observed between carriage rates of children coming from medical and non-medical families and the average carriage rate was 42.6% when duration of day-care attendance exceeded 6 months. Our results demonstrate that Hib carriage rates are affected by the duration of DCC attendance. Parents' employment in a health care facility does not affect carriage rates.

A Case with Gaucher-Like Cells.

Gaucher-like cells (GLC) are sometimes indistinguishable from real Gaucher cells. GLC can be detected in various diseases. We present a 4.5 year old boy with massive cervical lympadenopathy and an intraabdominal mass mimicking lymphoma. Many GLC were seen in the fine needle aspiration material of an enlarged lymph node. Ziehl-Neelsen stain of the aspirate revealed many acid-fast bacteria in the GLC. Fine needle aspiration might provide valuable information in the evaluation of enlarged lymph nodes.

Local and systemic reactions during immunotherapy with adsorbed extracts of house dust mite in children.

BACKGROUND: We retrospectively evaluated the incidence of local and systemic reactions to injections of adsorbed extracts of house dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae) applied according to a conventional schedule in children. METHOD: Eighty-eight patients aged 6 to 15 years, suffering from allergic asthma or asthma together with rhinitis, at various stages of treatment with immunotherapy from January 1989 to November 1997 were included. RESULTS: Out of 5,760 injections, 5,542 (96.21%) were not associated with a reaction, 206 injections (3.57%) caused local reactions (144, <20 mm in diameter; 62, >20 mm), and systemic reactions were seen after 12 injections (0.2%). Twelve patients experienced 12 systemic reactions. Of these, 7 patients (58.3%) experienced no local reactions prior to a systemic reaction. Eleven males and one female had systemic reactions. Most of both local and systemic reactions occurred within less than 30 minutes after the injection. CONCLUSIONS: Our study supports the safety of immunotherapy with house dust mites in children. The majority of reactions were local. Although five of 12 patients who experienced systemic reactions had local reactions prior to a systemic reaction, in general the presence of local reactions was not helpful in predicting which patients would develop systemic reactions. Males and patients with asthma together with rhinitis appeared to be at greater risk for systemic reactions.

In a novel form of IFN-gamma receptor 1 deficiency, cell surface receptors fail to bind IFN-gamma.

Complete IFN-gamma receptor ligand-binding chain (IFNgammaR1) deficiency is a life-threatening autosomal recessive immune disorder. Affected children invariably die of mycobacterial infection, unless bone marrow transplantation is undertaken. Pathogenic IFNGR1 mutations identified to date include nonsense and splice mutations and frameshift deletions and insertions. All result in a premature stop codon upstream from the segment encoding the transmembrane domain, precluding cell surface expression of the receptors. We report herein two sporadic and two familial cases of a novel form of complete IFNgammaR1 deficiency in which normal numbers of receptors are detected at the cell surface. Two in-frame deletions and two missense IFNGR1 mutations were identified in the segment encoding the extracellular ligand-binding domain of the receptor. Eight independent IFNgammaR1-specific mAb's, including seven blocking antibodies, gave recognition patterns that differed between patients, suggesting that different epitopes were altered by the mutations. No specific binding of (125)I-IFN-gamma to cells was observed in any patient, however, and the cells failed to respond to IFN-gamma. The mutations therefore cause complete IFNgammaR1 deficiency by disrupting the IFN-gamma-binding site without affecting surface expression. The detection of surface IFNgammaR1 molecules by specific antibodies, including blocking antibodies, does not exclude a diagnosis of complete IFNgammaR1 deficiency.

Prevalence of bronchial asthma and allergic rhinitis in Istanbul school children.

The aim of this study was to determine the prevalence of asthma, allergic rhinitis and their related symptoms in Istanbul and to investigate the effect of socioeconomic status on the prevalence of asthma and allergic rhinitis and whether there are differences between the prevalence of childhood asthma in the same and different regions as found in previous studies and our own. The study period was the 1996-1997 school year in three primary schools in Istanbul. For proportional representation of high, middle, and low socioeconomic levels, the schools were selected from three different regions of Istanbul. A translated version of the International Study of Asthma and Allergies in Childhood (ISAAC) was used. The questionnaire was distributed to the parents of 2600 students aged 6-15 years. All of the 2276 children whose parents responded were included in the survey. The overall cumulative and current prevalences of wheezing were 13.7 and 7.2% respectively and the overall cumulative prevalence of allergic rhinitis was 17.6%. There was no statistically significant difference between asthmatics and non-asthmatics by sex, socioeconomic status and passive smoking. Family history of atopy was found to be significantly higher in asthmatics. Although there are differences in the results of studies concerning the prevalence of asthma and allergic rhinitis not only between different countries but also between different regions of the same city, by using a standardized international method, the actual values may be obtained.

Latex allergy: the incidence among Turkish children with atopic disease and with neural tube defects.

BACKGROUND: latex allergy occurs mainly in people exposed to latex products because of their occupation or because of repeated surgery. Atopy is a strong predisposing factor. Identification of latex sensitive individuals can be life saving. METHODS: to investigate the incidence of latex hypersensitivity, 212 children with atopic disease, 85 with neural tube defects and 200 normal children aged 2 to 14 years were interviewed and prick skin tests were performed. RESULTS: latex allergy was found in 10.8% of atopic children, 30.5% of children with neural tube defects, and 1% of normal children. Latex allergy incidence in operated children with neural tube defects was found 3.5 times more frequently in compare with non-operated patients. CONCLUSIONS: atopic children and children with neural tube defects should carefully be followed up for latex allergy specially if recurring itching, urticaria, eczema, rhinitis and eye symptoms are present.

Analysis of the CFTR gene in Turkish cystic fibrosis patients: identification of three novel mutations (3172delAC, P1013L and M1028I).

In order to determine the spectrum of cystic fibrosis (CF) mutations in the Turkish population, a complete coding region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene including exon-intron boundaries, on 122 unrelated CF chromosomes from 73 Turkish CF families was analysed by denaturing gradient gel electrophoresis and multiplex heteroduplex analysis on MDE gel matrix. In addition to 15 previously reported mutations and 12 polymorphisms, three novel mutations, namely 3172delAC, P1013L and M1028I, were detected. DeltaF508 was found to be present on 18.8% of CF chromosomes. The second most common mutation was 1677delTA, with a frequency of 7.3%, followed by G542X and 2183AA-->G mutations, with frequencies of 4.9%. These four most common mutations in Turkish CF population account for approximately 36% of mutations. This study could only detect 52.5% of disease-causing mutations in this population; 47.5% of CF alleles remain to be identified, reflecting the high molecular heterogeneity of the Turkish population.