RESUMO
Background: The subtelomeric rearrangements are increasingly being investigated in cases of idiopathic intellectual disabilities [ID] and congenital abnormalities [CA] but are also thought to be responsible for unexplained recurrent miscarriage [RM]. Such rearrangements can go unnoticed through conventional cytogenetic techniques and are undetectable even with high-resolution molecular cytogenetic techniques such as array comparative genomic hybridization [aCGH], especially when DNA of the stillbirth or families are not available. The aim of the study is to evaluate the rate of subtelomeric rearrangements in patients with RM
Materials and Methods: In this cross-sectional study, fluorescent in situ hybridization [FISH], based on ToTelVysion telomeric probes, was undertaken for 21 clinically normal couples exhibiting a "normal" karyotype with at least two abortions. Approximately 62% had RM with a history of stillbirth or CA/ID while the other 38% had only RM
Results: FISH detected one cryptic rearrangement between chromosomes 3q and 4p in the female partner of a couple [III:4] [46,XX,ish t[3;4][q28-,p16+;p16-,q28+][D3S4559+,D3S4560-,D4S3359+; D3S4560+, D4S3359- ,D4S2930+]] who presented a history of RM and family history of ID and CA. Analysis of the other family members of the woman showed that her sisters [III:6 and III:11] and brother [III:8] were also carriers of the same subtelomeric translocation t[3;4][q28;p16]
Conclusion: We conclude that subtelomeric FISH should be undertaken in couples with RM especially those who not only have abortions but also have had at least one child with ID and/or CA, or other clinically recognizable syndromes. For balanced and cryptic anomalies, subtelomeric FISH still remains the most suitable and effective tool in characterising such chromosomal rearrangements in RM couples
RESUMO
Background: Neuroblastoma [NB] shows a complex combination of genetic aberrations. Some of them represent poor genetic prognosis factors that require specific and intensive chemotherapy. MYCN amplification consists of the major bad outcome prognostic factor, it is indeed frequently observed in aggressive neuroblastomas. To date different methods are used for MYCN status detection
Objectives: The primary aim of our study was to provide a critical assessment of MYCN status using 2 molecular techniques CISH and MLPA. We also focused on the correlation between neuroblastoma genetic markers and patient's clinical course among 15 Tunisian patients
Methods: we developed a descriptive study that includes 15 pediatric Tunisian patients referred to our laboratory from 2004 to 2011. We reported the analysis of fresh and FFPE NB tumors tissues
Results:No significant correlation was found between COG grade and patients overall survival. Assessment of NMYC gene copy number by kappa statistic test revealed high concordance between CISH and MLPA tests [kappa coefficient = 0.02]
Conclusion: Despite misdiagnosing of MYCN status fewer than 5 copies, MLPA remains an effective molecular technique that enables a large panel of genomic aberrations screening. Thus combining CISH and MLPA is an effective molecular approach adopted in our laboratory. Our results allow pediatric oncologists to set up the first Neuroblastoma therapeutic strategy based on molecular markers in Tunisia