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A rapid and reliable chromosome analysis method for products of conception using interphase nuclei
- Source :
- Molecular Genetics & Genomic Medicine
- Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- Monosomy
medicine.medical_specialty
Karyotype
Aneuploidy
Chromosomal translocation
Trisomy
Computational biology
Biology
Sensitivity and Specificity
in situ hybridization
03 medical and health sciences
Cytogenetics
0302 clinical medicine
Pregnancy
Prenatal Diagnosis
Genetics
medicine
Humans
spontaneous
Molecular Biology
Interphase
Genetics (clinical)
In Situ Hybridization, Fluorescence
Chromosome Aberrations
030219 obstetrics & reproductive medicine
medicine.diagnostic_test
Original Articles
medicine.disease
abortion
Abortion, Spontaneous
Products of conception
030220 oncology & carcinogenesis
Karyotyping
Cytogenetic Analysis
Tetrasomy
Female
Original Article
fluorescence
Fluorescence in situ hybridization
Subjects
Details
- ISSN :
- 23249269
- Volume :
- 6
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Molecular geneticsgenomic medicine
- Accession number :
- edsair.doi.dedup.....73f18fe0108dd5f5431c6a8dc2a727c9