Cytogenomic Characterization of a Novel de novo Balanced Reciprocal Translocation t(1;12) by Genome Sequencing Leading to Fusion Gene Formation of EYA3/EFCAB4b .

Autor:	Dutta UR; Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India., Bhattacherjee A; Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India., Bahal A; Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India., Posanapally LP; Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India., Lone KA; Laboratory of Cell Cycle Regulation, Hyderabad, India., Bathula S; Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India., Dalal A; Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
Jazyk:	angličtina
Zdroj:	Molecular syndromology [Mol Syndromol] 2022 Dec; Vol. 13 (5), pp. 370-380. Date of Electronic Publication: 2022 Mar 16.
DOI:	10.1159/000522011
Abstrakt:	Introduction: The accurate detection of breakpoint regions of disease-associated chromosomal rearrangements helps understand the molecular mechanisms and identify the risks involved with disrupted genes. Methods: In this study, a girl with growth retardation is characterized using positional cloning and genome sequencing. The techniques include fluorescence in situ hybridization (FISH) with paint (WCP) and bacterial-artificial chromosomes (BAC) probes, PCR, real-time PCR, and short and long-read sequencing. Results: The translocation was identified by GTG banding and confirmed by WCP FISH. Microarray ruled out the involvement of other copy number variations except for 6 homozygous regions which are not disease-causing variants. Fine mapping with FISH showed split signals with BAC clone RP11-312A3. Genome sequencing of short-read with an average 30× depth and long-read sequencing technology with a 3.8× coverage identified both breakpoints, confirmed by Sanger sequencing, that showed microhomology. The breakpoint at 1p and 12p regions disrupted EYA3 and EFCAB4B genes. Expression analysis of EYA3 showed a 7-fold increase, suggesting the formation of a fusion gene with EFCAB4B . EYA3 is involved in skeleton development, and EFCAB4B plays a role in calcium metabolism, which may be relevant for the patient's phenotype. Conclusion: The systematic application of genome techniques to translocations and their advantages is discussed. Competing Interests: The authors declare no conflict of interest. (Copyright © 2022 by S. Karger AG, Basel.)
Databáze:	MEDLINE
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