Analysis of Xq27.3 Fragility Using the Micronucleus-Fluorescence In situ Hybridization Assay.

Chromosome fragile sites tend to form gap or break in chromosomes when the cells are exposed to replication stress. Folic acid deprivation in the culture medium induces folate-sensitive rare fragile sites, such as FRAXA which is responsible for the fragile X mental retardation syndrome. Chromosome instability at fragile sites can be evaluated by biomarkers of genomic instability such as frequency of micronuclei (MN). It was aimed to analyse the chromosome content of MN in Fragile X cells during folate deprivation by the MN-fluorescence in situ hybridization (FISH) method. Samples from five Fragile X syndrome patients, diagnosed using cytogenetic and molecular methods, as well as from their parents and five controls were included in the study. Blood samples were cultured in two different culture media (folate-deficient and normal). Results of MN-FISH test were analysed in terms of MN frequency and chromosome content of MN. An accumulation of MN in Fragile X patients, mainly containing T (+) or C (+) MN or T (+) plus C (+) MN in binucleated cells was found. Finally, MN-FISH analysis allowed confirming that the increase in MN frequency is due to a higher sensitivity to chromosome breakage along the X chromosome.

Chromosomal aberrations induced by radiotherapy in lymphocytes from patients with lung cancer.

In this study we tried to define incidence and types of chromosomal aberrations (CAs) caused by radiotherapy (RT) in circulating lymphocytes from patients with lung cancer. For this purpose, we used cumulative dose-effect relationship, and correlate these data with statistical parameters. CAs were evaluated in terms of chromosome break, dicentric, ring and chromosome gap. Abnormal metaphase number (AMN) was also calculated Chromosome studies were carried out in peripheral blood lymphocytes of 20 cancer patients receiving RT. Patients were treated with 10 Gy of gamma (gamma) radiation during five wk(s). In all patients, a significant increase in AMN and frequency of CAs (e.g. chromosome break, dicentric, ring and chromosome gap) observed during the RTdepend on cumulative radiation dose when compared to before RT, and this increase was statistically significant (p<0. 05). The highest CAs frequency was observed at the end of fifth wk. Among the CAs, chromosome breaks have a high incidence. But no CAs and abnormal metaphase was observed in lymphocytes before RT. The present study showed that RT possess a significant effect in increasing of CAs and chromosome break, dicentric, ring and chromosome gap are very sensitive and useful biomarkers in the study of this effect. In other words, these CAs may be used as possible fingerprints of RT.

Acute myeloid leukemia in Turkish children with Fanconi anemia. One center experience in the period between 1964-1995.

OBJECTIVE: Fanconi's anemia(FA) is an autosomal recessive disorder characterized by a progressive pancytopenia,variable congenital abnormalities and an increased risk for the development of acute myeloid leukemia (AML). The objective of this study is to evaluate AML in the patients with FA diagnosed and followed-up in the Department of Pediatric Hematology at Ankara University School of Medicine in the period between 1964-1995. METHODS: A total of 39 patients within the age range 2-14 years( mean 8.2±3.16),28 male and 11 female were diagnosed as FA on the basis of congenital abnormalities,pancytopenia, bone marrow hypoplasia and diepoxybutane induced chromosomal abnormalities that observed in all patients The hereditary and familial basis of FA was apparent in this series.Common abnormalities were growth retardation,cefe'- au- laitspots,hyperpigmentation,microcephaly, finger and thumb deformities,mental retardation and hypogenitalismus RESULTS: Four AML (10.2%) were observed in our series.Cytogenetic analysis of these cases revealed 46/ XX,dup(3)(q22;q26) t(7;17) (p11;p11) in one where it was unsuccessful in three.Two cases could not achieve remission and died.The other two achieved complete remission and remained in remission for2 and 6 months. CONCLUSION: Acute myelomonocytic type in three cases and acute monocytic type in one patient were diagnosed in our series. The patients with FA should be followed with regard to AML and solid tumors. AML and solid tomors should be taken into the consideration as the first manifestation of FA.

The role of genetic counseling on decisions of pregnant women aged 35 years or over regarding amniocentesis in Turkey.

We investigated the effects of genetic counseling given before amniocentesis that is given based on maternal serum screening (using the cut-off value of 1/250) and genetic sonogram results (+/- abnormal ultrasound marker) on pregnant women who are 35 years and older age. Their attitudes towards amniocentesis after genetic counseling were evaluated. Among 340 women, 223 (65.6%) were in the high-risk group and 117 (34.4%) were in the low-risk group according to non-invasive test results. After counseling, 216 pregnant women (167 cases have high-risk, 49 cases who had low-risk) decided to have amniocentesis while 124 women (56 with high-risk and 68 with low-risk) declined it. Fourteen abnormal karyotypes were detected. All pregnant women who had fetuses with chromosomal aberrations were in high-risk group. Our study shows that screening by non-invasive prenatal diagnostic tool has an effect on families' choice of amniocentesis. The use of these test results during counseling decreased the number of amniocentesis in a ratio of 36.5%.

The impact of vitamin D receptor genotype on the management of anemia in hemodialysis patients.

BACKGROUND: Both in vitro and in vivo studies have shown that calcitriol, the active form of vitamin D, is involved in hematopoiesis. We hypothesized that the vitamin D receptor (VDR) genotype, which may differentiate response to endogenous or exogenous active vitamin D, has a role in the management of anemia in hemodialysis (HD) patients. METHODS: The VDR BsmI gene polymorphism was determined in 91 HD patients and 85 healthy controls. In addition to well-known factors responsible for both anemia and inadequate response to erythropoietin (EPO), we examined the contribution of the VDR genotype to hematocrit (Hct), hemoglobin (Hb) level, total weekly dose of EPO, and EPO-Hb ratio as an index of patient EPO need. RESULTS: Genotype distributions for the VDR gene were under the Hardy-Weinberg equilibrium and similar in patients and controls (genotypes BB, Bb, and bb: 22.0%, 38.5%, and 39.5% in patients versus 24.7%, 48.2%, and 27.1% in controls). There were statistically significant differences in Hct, Hb level, EPO dose, and EPO-Hb ratio in patients with the three BsmI genotypes, whereas the other parameters were the same. Comparison of patients with an Hb level less than versus greater than 11 g/dL showed that the former patients had lower albumin levels (P = 0.001), higher C-reactive protein levels (P = 0.014), and a greater frequency of BB genotype (P < 0.001). Similarly, comparison of patients with an EPO-Hb ratio in the highest quartile versus those in the lowest quartile showed that the former patients had lower albumin and transferrin levels (P = 0.013 for both) and greater frequencies of BB genotype (P = 0.016). In logistic regression analysis, both BB genotype and low serum albumin level were found to be the only independent predictors for an Hb level less than 11 g/dL (P < 0.001 and P = 0.046, respectively). Both parameters also predicted being in the highest quartile of EPO-Hb ratio (P = 0.004 for both). CONCLUSION: The VDR BsmI gene polymorphism may predict both Hb level and EPO need in HD patients. However, because the underlying mechanisms have not been clarified in the present study, further research on this issue is needed.

Common fragile sites associated with the breakpoints of chromosomal aberrations in hematologic neoplasms.

Fragile sites are specific regions of chromosomes prone to breakage when cells are cultured under specific conditions. These sites are divided into two classes: common and rare. Common fragile sites are expressed in all individuals at different frequencies, whereas rare ones are found only in certain individuals. Common and rare fragile sites have been shown to display a number of characteristics of instability being preferential sites for chromosomal deletions, duplications, and rearrangements. Moreover, a majority of mapped oncogenes are located at or near these fragile sites. These observations have led to the suggestion that both classes of fragile sites may play a significant role in chromosomal rearrangements involved in oncogene activation or tumor supressor gene inactivation. For these reasons, involvement of common and rare fragile sites and their relevance to specific chromosome breakpoints in cancer have received much attention. In this study, which reports on the cytogenetic findings obtained from 256 patients with chronic myelocytic leukemia, 103 with acute myelocytic leukemia, 40 with acute lymphocytic leukemia, 33 with myelodysplastic syndrome, we documented the fragile sites involved in chromosomal aberrations involving oncogenes, tumor supressor genes, and other known genes important in cell cycle regulation localized at these sites.

Y-STR polymorphism in Central Anatolian Region of Turkey.

Eight Y-chromosome specific STR (Y-STR) loci including DYS19, DYS388, DYS389I, DYS389II, DYS390, DYS391, DYS392 and DYS393 were investigated in a group of males from Central Anatolian Region of Turkey. Healthy 59 males living in this region for at least three generations were included in the study. PCR analysis was carried out with Y-STR specific primers on genomic DNA obtained from peripheral blood samples and size determination of PCR products was performed by silver staining following 6% polyacrylamide gel electrophoresis (PAGE). DYS388 was found to be the locus with lowest diversity (D) whereas DYS389II was the locus with highest diversity. The current study presented a framework of variation for the eight Y-STR loci in Central Anatolian population.

The relationship between angiotensin converting enzyme gene I/D polymorphism and QT dispersion in patients with hypertrophic cardiomyopathy.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is characterized by disorganized myocardial architecture, and may cause ventricular arrhythmias and sudden death. The angiotensin-converting enzyme (ACE) with two deletion alleles (DD genotype) has been proposed to be associated with increased myocardial collagen content. We evaluated QT dispersion (QTd), which reflects regional differences in ventricular repolarization, in HCM patient and controls among the three different ACE genotypes. MATERIALS AND METHODS: Sixty-three patients with HCM and 20 healthy subjects were included in the study. QT parameters were measured from 12 lead electrocardiograms. ACE genotypes were determined from the DNA extracted from peripheral blood by a polymerase chain reaction (PCR) method. QT parameters were compared among the three ACE genotypes both in HCM patients and controls. RESULTS: Median ages were similar in HCM and control groups. QTd and corrected QTd (QTcd) were significantly greater in the HCM group compared with the controls. The frequencies of each genotype were similar in both groups. Although QTd and QTcd did not differ among the three genotypes in the control subjects, they were significantly greater in patients with DD genotype compared with other genotypes in the HCM group. CONCLUSION: QTd and QTcd are increased in patients with HCM, especially in those with the DD genotype.

An unusual combination: aortic arch coarctation associated with Dandy-Walker variant.

We report on a 29-year-old woman with aortic arch coarctation with cerebral anomalies including posterior fossa cyst, hydrocephalus, cerebellar vermis hypoplasia and multiple congenital anomalies including hirsutism, hipotelorism, shortened philtrum, unregulated teeth and short alveolar crest, rotated auricles, short and webbed neck, hypopigmentation on the scalp, bilateral clinodactyly, bilateral hallux valgus, brachydactyly on the left foot 3rd finger, hemangioma on the sacrum. An extra-anatomical bypass was made by grafting from the ascending to the distal descending aorta. Some of these features are consistent with the diagnosis of the other clinical syndromes except genetical expression, no chromosomal deletions in our patient with normal familial pedigree, however, cerebral anomalies are consistent with the Dandy-Walker variant. To the best of our knowledge, literature contains no other report of the association of aortic coarctation, Dandy-Walker variant with these clinical features. These previously undescribed combinations, however, raise the possibility of a newly recognized disorder.

A 15-year-old boy with Rubinstein-Taybi syndrome associated with severe congenital malalignment of the toenails.

Rubinstein-Taybi syndrome (RTS) is a well-known disorder characterized by growth and mental retardation, typical facial features, short stature, and broad thumbs and toes. Although several cutaneous manifestations are observed in these patients, they are not diagnostic and are usually considered to be coincidental. Congenital malalignment of the great toenails is a very rare disorder that is characterized by lateral deviation of the nail plate along its longitudinal axis. The nail plate grows into the lateral nail fold resulting in pain and infection. It is usually present at birth or begins in early childhood. We report a patient with characteristic manifestations of RTS and congenital malalignment of the great toenails. The association of these two entities has not been reported previously.

Is SHORT syndrome another phenotypic variation of PITX2?

Even though responsible genetic loci and mode of inheritance for the Rieger syndrome have been well established, the mode of inheritance and the genetic basis for SHORT syndrome are still uncertain. The purpose of this paper is to document a familial translocation of t(1;4)(q31.2;q25), in a mother and her son manifesting Rieger syndrome with polycystic ovaries and SHORT syndrome, respectively. It is suggested that these two syndromes may be different expressions of the same gene, PITX2, localized at 4q25. Our patient is the second with the association of Rieger syndrome and polycystic ovaries, and thus this may not be coincidental, moreover insulin resistance-related phenotypes, such as lipodystrophy and polycystic ovaries, can be major component of syndromes with Rieger eye malformation.