Hyperphosphatemic familial tumoral calcinosis caused by a novel variant in the GALNT3 gene.

AIM: Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare endocrine disorder caused by autosomal recessive variants in GALNT3, FGF23, and KL leading to progressive calcification of soft tissues and subsequent clinical effects. The aim of this was to study the cause of HFTC in an Iranian family. PATIENTS AND METHODS: Four generations of a family with HFTC were studied for understanding the genetic pattern of the disease. Whole exome sequencing was applied on genomic DNA of the proband. Based on its result, genetically altered sequences were checked in his family through sanger sequencing. Then bioinformatics approaches as well as co-segregation analysis were applied to validate the genetic alteration. RESULTS: A novel homozygous variant in exon four of GALNT3, namely p.R261Q was found. The parents and sister were carriers. CONCLUSION: To our knowledge, it is the first-reported Iranian family with GALNT3-CDG novel variant.

A case with 46,XX,del(11)(q23.2) karyotype and poor vision with literature review.

Here we describe clinical and cytogenetic data on a female child whom had been referred to our laboratory suspected to have Turner syndrome since she had webbed neck. Cytogenetic analysis revealed that she had deletion at 11q23.2 to 11q terminal so her karyotype was ascertained as 46,XX,del(11)(q23.2). Her parents had normal karyotypes. In addition to many clinical features of del(11q ) syndrome the case had poor vision which is not common for this syndrome. Clinical features of this case and a few published cases will be reviewed briefly.

Constitutional complex chromosomal rearrangements in a klinefelter patient: case report and review of literature.

BACKGROUNDS: While XXY aneuploidy is the most common disorder of sex chromosomes in men, complex chromosomal rearrangements (CCRs) are rare in humans. CASE DESCRIPTION: Here we describe clinical and cytogenetic findings in a male referred to our cytogenetic laboratory by an infertility clinic. The patient's age was 35 at the time of referral. Total azoospermia was confirmed on semen analysis. RESULTS: The karyotype of peripheral blood showed 47,XXY,t(1;3;5)(p22;q29;q22). The mother had the same CCRs. DISCUSSION: To our best of our knowledge this is the first case of 47,XXY with CCRs. We think it is important to report such a unique chromosomal occurrence.

Concurrence of inv(7)(q11.2q32) and del(8)(p23.1) in a girl with congenital microcephaly, hypotonia, developmental delay, strabismus, hypernatremia, hypermagnesemia and deafness.

The clinical manifestations and cytogenetic details of a de novo partial deletion of the short arm of chromosome 8, del(8)(p23.1), and inversion of long arm chromosome 7, inv(7)(q11.2q32), are described. The case was a 22 month old girl referred to our cytogenetic laboratory due to many abnormal features such as congenital microcephaly, hypotonia, developmental delay, strabismus, highly arched palate, hypernatremia, hypermagnesemia and deafness. Chromosome analysis revealed 46,XX, inv(7)(q11.2q32),del(8)(p23.1) de novo karyotype. The concurrence of these two abnormalities has not been reported previously.

A novel missense mutation in exon 7 of the ECM1 gene in an Iranian lipoid proteinosis patient.

Lipoid proteinosis (LP) is a rare autosomal recessive disorder. Classical clinical features include warty skin infiltration, papules on the eyelids, skin scarring, as well as extracutaneous abnormalities such as hoarseness of the voice, epilepsy, and neuropsychiatric abnormalities. A defect in the ECM1 gene is responsible for this disease. A 21-year-old female patient from consanguineous parents (first cousins) was referred to our clinic with many symptoms of LP, such as hoarse voice from infancy, diffuse acneiform scars on her face, and hyperkeratosis on her knees and elbows. The entire ECM1 gene was screened using PCR and sequencing. A novel missense mutation was found in exon 7 of this patient. We report a novel missense mutation in exon 7 of the ECM1 gene found in an Iranian LP patient that causes a C269Y amino acid exchange.

Cytogenetic findings in mentally retarded Iranian patients.

We conducted a cytogenetic study on 865 individuals with idiopathic mental retardation (MR) who were admitted to the Cytogenetics Department of the Iran Blood Transfusion Organisation (IBTO) Research Centre, Tehran, Iran; these were performed on blood samples using conventional staining methods. Chromosome anomalies were identified in 205 of the patients (23.6%). The majority were Down's syndrome cases (n = 138). In 33 males, a positive fragile X anomaly was found. The remainder (n = 34) had other chromosomal abnormalities including structural chromosome aberrations (n = 23), marker chromosomes with an unknown origin (n = 3), sex chromosome aneuploidy (n = 6) and trisomy 18 (n = 2). The contribution of chromosome aberrations to the cause of MR in this group of patients is discussed.

Partial Trisomy 9p(p22→pter) from a Maternal Translocation 4q35 and 9p22.

We present clinical and cytogenetic data on a 7-year-old female child with partial trisomy for 9p22→9pter as a result of a maternal balanced reciprocal translocation. Her karyotype was ascertained as 46,XX,dec(4)t(4;9)(q35; p22)mat. The father had a normal karyotype, while the mother had an apparently balanced translocation involving chromosomes 4 and 9 [46,XX,t(4;9)(q35;p22)]. This case will be briefly compared with other published cases of a similar translocation.

Effect of MDR1 polymorphism on multidrug resistance expression in breast cancer patients.

One of the limitations in the treatment of cancer patients with chemotherapy is the development of multidrug resistance (MDR). A well-known mechanism responsible for drug resistance is over-expression of ABC-transporter genes such as MDR1. This gene encodes p-glycoprotein (P-gp), a transmembrane glycoprotein that transports many hydrophobic substrates and anti-cancer drugs out of the cell. MDR1 gene polymorphisms could alter the expression level of P-gp and consequently result in drug resistance. We investigated a possible association between MDR1 gene C3435T polymorphism and its expression in Iranian breast cancer patients. PCR-RFLP was used for the detection of C3435T single nucleotide polymorphism in 54 breast cancer patients and 50 healthy individuals. The expression level of MDR1 was determined by real-time quantitative PCR. We observed no difference in the frequency of C3435T polymorphism between breast cancer patients and healthy controls. However, there was a significant association between MDR1 expression levels and C3435T polymorphism in the patients. C3435T polymorphism may play a role in inducing drug resistance by altering the expression level of the MDR1 gene.

MRP1 polymorphisms (T2684C, C2007T, C2012T, and C2665T) are not associated with multidrug resistance in leukemic patients.

One of the main problems in treating cancer patients is that cancer cells can develop drug resistance. Resistance to multiple anticancer drugs, so called multidrug resistance (MDR), most likely involves a nonspecific mode of resistance, through drug-efflux transporters. One of the most extensively studied genes involved in MDR is multidrug resistance protein 1 (MRP1). We investigated a possible association between the expression level of MRP1 and the occurrence of MDR in leukemic patients, and we tested the hypothesis that MRP1 polymorphisms are predictive of MDR in patients with acute leukemia. The mRNA level of MRP1 was determined in 111 patients with acute leukemia (including 52 patients with acute myeloid leukemia and 59 patients with acute lymphoblastic leukemia), by quantitative real-time PCR, to determine how it affected the response to chemotherapy. We typed T2684C, C2007T, C2012T, and C2665T MRP1 polymorphisms in 111 patients classified as either drug-resistant or drug-responsive. We found that high expression of MRP1 was associated with the MDR phenotype in both acute myeloid leukemia and acute lymphoblastic leukemia patients. There was no effect of a particular genotype on the expression level of the MRP1 gene. We found no significant differences in chemosensitivity among any of these genotypes.

[Resistance to third generation cephalosporins in Sfax hospitals, Tunisia (1999-2005)]. / Etude de la résistance des entérobactéries aux céphalosporines de troisième génération dans les hôpitaux de Sfax, Tunisie (1999-2005).

OBJECTIVES: The authors wanted to assess the prevalence and to monitor the trends of resistance to broad-spectrum cephalosporins among various species of enterobacteria in the region of Sfax (Tunisia). METHODS: A retrospective study was carried out in the microbiology laboratory at the Habib-Bourguiba Teaching Hospital in Sfax. Data concerning a seven-year period (1999-2005) were analyzed with the Whonet 5.4 software. All clinical isolates of enterobacteria were identified with the API 20 E system. Antimicrobial susceptibilities were determined by disk diffusion on Mueller Hinton agar according to CA-SFM recommendations. RESULTS: During the study period, 24,702 non-duplicate clinical strains of enterobacteria were identified. Fifteen percent (3,826) clinical isolates showed acquired resistance to third generation cephalosporins (3rdGC). The overall frequency of resistance increased from 10% in 1999 to 18% in 2005. This increase was statistically significant. High prevalence rates of 3rdGC resistance have been observed in intensive care units (48%), hematology and oncology wards (27%) and pediatric wards (25%). Klebsiella pneumoniae, Indole positive Proteus and Enterobacter showed high prevalence rates of broad-spectrum cephalosporin resistance. CONCLUSION: This study revealed a high rate of 3rdGC resistance enterobacteria in our region, particularly in intensive care units. The frequency of acquired resistance to broad-spectrum cephalosporins seemed to be increasing. Implementation of infection control measures and identification of the mechanism responsible for third generation cephalosporins resistance are necessary to limit the spreading of these resistant enterobacteria in hospitals and community settings.

[Prognostic factors of pneumococcal meningitis. Retrospective study of 31 cases]. / Facteurs de pronostic des méningites à pneumocoque. Etude rétrospective de 31 cas.

AIM: Our aim was to study the susceptibility of Streptococcus pneumoniae to antibiotics in patients with pneumococcal meningitis and to search for the prognosis factors in those patients. METHODS: We have studied retrospectively 31 cases of pneumococcal meningitis. Comparaisons were performed with univariate analysis. RESULTS: The mean age was 36.7 +/- 20.5 years (ranged: 9 and 78 years). The sex ratio was 3,4. The susceptibility of Streptococcus pneumoniae to penicillin G was affected in 10 cases (33% of isolated pneumococcus. The MIC to penicillin G was > or =2 in only one case. The hospital mortality was 26% (8/31). With univariate analysis, factors associated with death were: age > or =55 years (Ss p= 0,006, OR: 17.2 IC95%: 2.3-134), albuminorachie > or = 7 g/l (p = 0.002, OR: 22; IC95%: 1.9-2.51), shock (p = 0.031, OR: 6.7; IC95%: 1.05-42) and Glasgow Coma Score (GCS) < or =8 (p = 0.001, OR: 20; IC95%: 2.68-149). CONCLUSION: No susceptibility to penicillin G is not associated with a worse outcome in patients with pneumococcal meningitis. An age > or =55 years, albuminorachie > or =7 g/l shock and Glasgow Coma Score < or =8 at admission were determinant of the prognosis in our study.

Micronucleus, Nucleoplasmic Bridge, and Nuclear Budding in Peripheral Blood Cells of Workers Exposed to Low Level Benzene.

BACKGROUND: Benzene is one of the important occupational pollutants. There are some reports about the leukemogenic effects related to low-level exposure to benzene. OBJECTIVE: To study the frequency of micronucleus (MN), nucleoplasmic bridge (NB), and nuclear budding (NBUD) in the peripheral blood lymphocytes of petrochemical workers with low level exposure to benzene. METHODS: We enrolled 50 workers exposed to low-level benzene and 31 unexposed workers of a petrochemical industry. After exclusion of 3 samples, peripheral blood lymphocytes of the remaining 47 exposed and 31 unexposed workers were analyzed for the frequency of MN, NB, and NBUD by cytochalasin-blocked MN technique. RESULTS: MN was present in 28 (60%) exposed and 18 (58%) unexposed workers. NB was observed in 6 (13%), and 2 (7%) exposed and unexposed workers, respectively; the frequency for NBUD was 20 (43%), and 13 (42%), respectively. No significant difference was found in the observed frequencies of MN, NB, and NBUD in the peripheral blood lymphocytes between the exposed and unexposed group workers. CONCLUSION: Occupational exposure to low-level benzene does not increase the frequency of MN, NB, and NBUD in the peripheral blood lymphocytes, biomarkers for DNA damage.

An analphoid marker chromosome inv dup(15)(q26.1qter), detected during prenatal diagnosis and characterized via chromosome microdissection.

A small, mosaic, C-band negative marker chromosome was detected in amniocyte cultures during prenatal diagnosis due to advanced maternal age. Following spontaneous premature labor at 29 weeks gestation, a dysmorphic infant was delivered, with flat nasal bridge, short palpebral fissures, micrognathia, high forehead, low-set ears, telecanthus and corneal dystrophy. Additional folds of skin were present behind the neck, and feet, fingers and toes were abnormally long. The child died at age five days, after two days of renal failure. The origin of the marker chromosome was subsequently identified from a cord blood sample, via chromosome microdissection. Through reverse FISH, we found the marker to be an inverted duplication of the region 15q26.1-->qter. FISH with alphoid satellite probe was negative, while whole chromosome 15 paint was positive. Both ends of the marker chromosome were positive for the telomeric TTAGGG probe. These data, plus the G-banding pattern, identified the marker as an analphoid, inverted duplicated chromosome, lacking any conventional centromere. We discuss the etiology and clinical effects of this marker chromosome, comparing it to the few reported cases of "tetrasomy 15q" syndrome. We also discuss the possible mechanisms that are likely responsible for this neocentromere formation.

[Predictive value of pericatheter skin cultures in detecting catheter-related infections in a medical-surgical intensive care unit]. / Apport diagnostique de l'écouvillonnage de la zone d'insertion cutanée dans l'exploration des infections liées aux cathéters veineux centraux dans un service de réanimation médicochirurgicale.

OBJECTIVE: To evaluate the predictive value of pericatheter skin cultures in detecting catheter-related infections in critically-ill patients. STUDY DESIGN: Prospective study. PATIENTS AND METHODS: Over a 5 months period (from August 1(st) 2001 to December 31 2001), 500 patients were hospitalised, and 108 central venous catheters were prospectively examined. For each catheter, blood cultures, pericatheter skin cultures and semiquantitative culture of the catheter tip were performed. RESULTS: The median duration of catheterization was 8 days (interquartile: 8 days). Catheter was removed because of suspected infection in 54 cases (50%). Systemic catheter-related infection was found in 12 cases (11%) and the responsible organism was a gram-negative rod in 11 cases (92%). The negative predictive values of pericatheter skin cultures in the diagnosis of catheter-related infections and in case of suspected catheter-related infection were 89 and 86%, respectively. CONCLUSION: These results indicate that the pericatheter skin cultures are not an effective procedure for the conservative diagnosis of catheter-related infections and that the skin-insertion wound is not the major source of catheter-contamination in our unit.

Evaluation of a cefoxitin disk diffusion test for the routine detection of methicillin-resistant Staphylococcus aureus.

Two oxacillin disk methods were compared with a cefoxitin disk diffusion test for detection of methicillin-resistant Staphylococcus aureus (MRSA), with PCR for mecA as the reference method. When tested with 115 MRSA and 350 methicillin-susceptible S. aureus isolates, the cefoxitin disk test (specificity 100%, sensitivity 96.5%) was superior to the oxacillin disk methods (specificity 99.1%, sensitivity 90.4%). Testing with both oxacillin and cefoxitin disks would give better sensitivity (100%) than the cefoxitin test alone, but at the expense of specificity (99.1%). The cefoxitin disk test required no special test conditions and would improve the reliability of routine tests for detection of MRSA.

[Intestinal parasitism in the adult. Evaluation of 2 years in the University Hospital Center of Sfax]. / Le parasitisme intestinal de l'adulte. Bilan de deux ans dans le Centre Hospitalo-Universitaire de Sfax.

From copro parasitologic analyses of two years studied between December 1988 and 1990 in the Hospital Center of the University of Sfax, the authors determined the intestinal parasites profile observed in adults. This intestine parasitism is mainly of protozoair type dominated by the amebae and Giardia intestinalis. The helminthes are rarely found. Strongyloides stercoralis of an epidemiology unknown in the region was revealed in some patients submitted to an immunosuppressive therapy. The adult cestodes as well as in Child doesn't seen to constitute a major parasitism in Sfax.

Epidemiological study of Enterobacteriaceae resistance to colistin in Sfax (Tunisia).

OBJECTIVES: The authors had for aim to monitor Enterobacteriaceae resistance to colistin, during 6 years (2005-2010), and to study the epidemiology of Enterobacteriaceae resistant strains isolated in the Sfax region (Tunisia). DESIGN: This retrospective study was carried out in the microbiology laboratory, at the Habib Bourguiba teaching hospital in Sfax. All strains of colistin resistant Enterobacteriaceae isolated from patients were studied. RESULTS: One hundred and twenty one strains of colistin resistant Enterobacteriaceae were isolated from 93 patients. Klebsiella pneumoniae was the most frequent species (60.2%), followed by Enterobacter cloacae (26.9%), and Escherichia coli (12.9%). Thirteen strains (E. cloacae) were heteroresistant to colistin. Eighty one isolates (87.1%) were resistant to third generation cephalosporins. The rate of resistance to colistin ranged from 0.09% for E. coli to 1.2% for K. pneumoniae, and 1.5% for E. cloacae. A progressively increasing colistin resistance was observed for K. pneumoniae. Most resistant strains were isolated from urine in the urology department. Previous exposure to colistin was reported in 59.2% of patients. Pulsed field gel electrophoresis typing revealed different clones. CONCLUSIONS: Colistin resistance in Enterobacteriaceae is a worrying phenomenon in Sfax. It is related to polyclonal diffusion. Continuous epidemiological monitoring and a rational use of colistin are necessary to limit the spreading of these colistin resistant strains and to maintain this antibiotic's effectiveness.