Parental somatic mosaicism for CNV deletions - A need for more sensitive and precise detection methods in clinical diagnostics settings.
Clinical diagnostic testing
Copy-number variant (CNV)
Mosaicism carrier
Parental somatic mosaicism
Recurrence risk
Journal
Genomics
ISSN: 1089-8646
Titre abrégé: Genomics
Pays: United States
ID NLM: 8800135
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
31
03
2020
revised:
22
04
2020
accepted:
04
05
2020
pubmed:
11
5
2020
medline:
19
8
2021
entrez:
11
5
2020
Statut:
ppublish
Résumé
To further assess the scale and level of parental somatic mosaicism, we queried the CMA database at Baylor Genetics. We selected 50 unrelated families where clinically relevant apparent de novo CNV-deletions were found in the affected probands. Parental blood samples screening using deletion junction-specific PCR revealed four parents with somatic mosaicism. Droplet digital PCR (ddPCR), qPCR, and amplicon-based next-generation sequencing (NGS) were applied to validate these findings. Using ddPCR levels of mosaicism ranged from undetectable to 18.5%. Amplicon-based NGS and qPCR for the father with undetectable mosaicism was able to detect mosaicism at 0.39%. In one mother, ddPCR analysis revealed 15.6%, 10.6%, 8.2%, and undetectable levels of mosaicism in her blood, buccal cells, saliva, and urine samples, respectively. Our data suggest that more sensitive and precise methods, e.g. CNV junction-specific LR-PCR, ddPCR, or qPCR may allow for a more refined assessment of the potential disease recurrence risk for an identified variant.
Identifiants
pubmed: 32387503
pii: S0888-7543(20)30340-2
doi: 10.1016/j.ygeno.2020.05.003
pmc: PMC7363577
mid: NIHMS1594354
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2937-2941Subventions
Organisme : NICHD NIH HHS
ID : R01 HD087292
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest BCM and Miraca Holdings Inc. have formed a joint venture with shared ownership and governance of Baylor Genetics (BG), formerly the Baylor Miraca Genetics Laboratories (BMGL), which performs chromosomal microarray analysis and clinical exome sequencing. JAR, CAB, SRL, AP, JLS, SWC and WB are current employees of BCM and derive support through a professional service agreement with BG. JRL has stock ownership in 23andMe, is a paid consultant for Regeneron Pharmaceuticals, and is a co-inventor on multiple US and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The remaining authors declare that they have no competing interests.
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