Complex rearrangement in acute myeloid leukemia M2 with RUNX1/RUNX1T1 fusion involving chromosomes 8, 17 and 21.

BACKGROUND: The translocation t(8;21)(q22;q22) is one of the most frequent chromosomal abnormalities associated with acute myeloid leukemia (AML) sub type M2. About 3-5 % of cases with additional chromosomal abnormalities, including structural and numerical ones, are reported to include a complex translocation t(8;21;N). CASE PRESENTATION: Here we report a chromosome rearrangement observed in a 19 years-old female diagnosed with AML-M2. When subjected to (molecular) cytogenetic analyses a complex three-way translocation involving chromosomes 8, 17 and 21 was detected, forming not a t(8;21;17) as one would expect. Real time-polymerase chain reaction analysis using 6 AML specific markers showed the presence of RUNX1/RUNX1T1 fusion gene transcripts identical to those found in classical translocation t(8;21) coupled with presence of FLT3-ITD mutation identified by fragment analysis. CONCLUSIONS: The present case highlights importance of complex rearrangements rarely encountered in AML, suggesting that all involved regions harbor critical candidate genes regulating the pathogenesis of AML, leading to novel as well as well-known leukemia associated chromosomal aberrations.

Clinical Manifestations of Chromosomal Anomalies and Polymorphic Variations in Patients Suffering from Reproductive Failure.

BACKGROUND: Human reproduction is the most intricate event as ~ 20% of human pregnancies end in miscarriages for which chromosomal anomalies are a common factor. The chromosomal variations associated with reproductive failures include translocations, inversions, supernumerary marker chromosomes, heterochromatic polymorphisms, etc., Till date, the significance of heteromorphic variants in reproductive failures is unclear. AIM: The aim of this study is to investigate the role of chromosomal anomalies and polymorphic variations in reproductive failure. MATERIALS AND METHODS: Chromosomal analysis using GTG banding was performed on 638 couples (1276 individuals). RESULTS: In the present study, 138 of 1276 individuals showed chromosomal variations with respect to heterochromatic variants and Robertsonian translocations. The most common variants observed across the population studied were the pericentric inversion of the chromosome 9 [inv(9)(p11q13), 3.68%] followed by pstk + on the short arm of chromosome 15 (15pstk+, 1.95%) and Robertsonian translocation of chromosomes 13 and 14 [rob(13;14)(q10;q10), 1.25%]. The maximum percentage of heterochromatic variation was observed in females with recurrent pregnancy loss (Groups A, 4.78%) and males with wives having recurrent miscarriages (Group B, 3.68%) and the minimum was recorded in patients with in vitro fertilization (IVF) failures (Group C, 0.23%) and couples having a history of the malformed child (Group F, 0.23%). CONCLUSIONS: High level of chromosomal polymorphic variations in patients with reproductive failures warrants their in-depth analysis to nail down the causative factors. Hence, cytogenetic analysis coupled with genetic counseling becomes indispensable for patients suffering from infertility, reproductive failures and pregnancy losses before IVF treatment to rule out the carrier status.

A rapid and reliable chromosome analysis method for products of conception using interphase nuclei.

BACKGROUND: Karyotype determination has a central role in the genetic workup of pregnancy loss, as aneuploidy (trisomy and monosomy) and polyploidy (triploidy and tetraploidy) are the cause in at least 50% of first trimester, 25% of second trimester, and 11% of third trimester miscarriages. There are several limitations with the current approaches of obtaining a karyotype using traditional cytogenetics, fluorescence in situ hybridization with a limited number of probes, and chromosomal microarray. These include culture failure, incomplete results, lower sensitivity, and longer reporting time. METHODS: To overcome current limitations, a novel molecular assay is developed with a Standard Resolution Interphase Chromosome Profiling probe set which is a variation of the recently developed High Resolution probe set. It generates a molecular karyotype that can detect all major changes commonly associated with pregnancy loss. Initial familiarization of signal patterns from the probe set was used, followed by validation of the method using 83 samples from miscarriages in a blind study from three different laboratories. Finally, the clinical utility of the method was tested on 291 clinical samples in two commercial reference laboratory settings on two different continents. RESULTS: The new molecular approach not only identified all the chromosome changes observed by current methods, but also significantly improved abnormality detection by characterizing derivative chromosomes and finding subtle subtelomeric rearrangements, balanced and unbalanced. All Robertsonian translocations were also detected. The abnormality rate was 54% on clinical samples from commercial laboratory 1 and 63% from laboratory 2. CONCLUSION: The attributes of this method make it an ideal choice for the genetic workup of miscarriages, namely (1) near 100% successful results, (2) greater sensitivity than conventional chromosome analysis or FISH panels, (3) rapid reporting time, and (4) favorable comparisons with chromosomal microarray.

Evaluation of the Protection Provided by Hepatitis B Vaccination in India.

OBJECTIVE: In India, Hepatitis B vaccination is recommended at 6 wk except for hospital-deliveries. The authors examined protection afforded by the birth dose. METHODS: A case-control study was done. HBsAg and HBcAb were tested in 2671 children, 1 to 5 y and HBsAb was evaluated in a subset of 1413 children. Vaccination history was recorded. Cases were HBsAg carriers. In another analysis, children who got infected (HBsAg and/or HBcAb positive) were considered as cases. Exposed were the unvaccinated. In another analysis, exposed were those vaccinated without the birth dose. RESULTS: The odds ratio (OR) for HBsAg positivity with birth vaccination was 0.35 (95% CI 0.19-0.66); while with vaccination at 6 wk was 0.29 (95%CI 0.14-0.61), both compared to unvaccinated. Birth vaccination has no added protection when compared to the unvaccinated. Unvaccinated children in index study had HBsAg positivity of 4.38%. The number needed to treat (NNT) to prevent one case of HBsAg positivity was 32.6 (95% CI, 20.9 to 73.6). The odds of getting HBV infection was 0.42 (CI 0.25-0.68) with birth dose and 0.49 (CI 0.30-0.82) without the birth dose compared to the unvaccinated. Protective antibody (HBsAb) was present in about 70% of the vaccinated. In the unimmunised, in the first 2 y HBsAb protection was present in 40%. The odds ratio (OR) for HBsAb in the fully vaccinated between 4 and 5 y was 1.4 (95%CI 0.9-2.18) compared to the unvaccinated. CONCLUSIONS: The present study lends support to the pragmatic approach of the Government to vaccinate babies born at home starting at 6 wk.

A rare case of mosaic 45,X/47,XX,+13 in 28-year-old women with secondary amenorrhoea: A case report and literature review.

In the present paper we report an extremely rare case of mosaicism of 45,X/47,XX,+13 in a 28-year-old women. The patient was referred for cytogenetic evaluation for secondary amenorrhoea. The patient was found to have some mild characteristic features of Turner syndrome such as wide carrying angle and short stature. Ultrasound examination revealed the presence of a small sized uterus and bilateral streak ovaries. G-banded chromosome analysis revealed a mosaic female karyotype involving two different cell lines. One cell line (72% of analysed metaphases) presented monosomy of X while the remaining 28% of cells showed trisomy of chromosome 13. Fluorescence in situ hybridization (FISH) with locus specific probe for trisomy 13 and CEP X for monosomy X substantiated the results obtained from karyotyping.