Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Determining the Cause of Recurrent Miscarriages in a Couple: Importance of NOR in the Era of NGS

Authors
Usha Dutta 1
Venugopala Swamy 1
Rajitha Ponnala 1
Shagun Aggarwal 2
Ashwin Dalal 1
1 Diagnostics Division, Center for DNA Fingerprinting and Diagnostics, Tuljaguda complex, Hyderabad, India
2 Department of Medical Genetics, Nizam’s Institute of Medical Sciences, Hyderabad, India; Diagnostics Division, Center for DNA Fingerprinting and Diagnostics, Tuljaguda complex, Hyderabad, India
Abstract
Background: Chromosomal abnormalities are a significant cause of human disorders. The characterization of such abnormalities helps in the identification of known/new genes. The purpose of the present study was to identify the cause of miscarriages in a couple by using combined molecular and cytogenetic techniques. Case Presentation: In this study, the clinical, cytogenetic and molecular cytogenetic evaluations were performed on a couple with recurrent miscarriages. Several methods like GTG banding, silver nitrate (NOR) staining, fluorescence in-situ hybridization (FISH) using whole chromosome paint probes (WCP) and bacterial artificial chromosome (BAC) clones were used. The chromosomal analysis on the metaphases revealed a karyotype of 46,XX in the wife and 46,XY,13p+ in her husband. To check the satellites on 13p region, NOR was performed which showed absence of satellites and presence of euchromatic material. On careful analysis, the satellites were observed on 11q terminal region. Thus, a balanced reciprocal translocation was detected which was confirmed by WCP and Acro-P-arm FISH. Fine mapping with BAC clones narrowed down the breakpoint regions. Conclusion: The application of the combined cytogenetic methods especially NOR helped in identification of the balanced reciprocal translocation with subsequent systematic characterization and the breakpoint regions were identified. The characterization of the breakpoint regions helped in identification of the carrier status which further paved the way for understanding the cause of recurrent miscarriages and proper genetic counseling.
Keywords
BAC clones
Bad obstetric history
fish
Nucleolar organizing regions
Satellites
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Journal of Reproduction & Infertility
Volume 20, Issue 2
Spring 2019
Pages 109-114