Highly Sensitive Blocker Displacement Amplification and Droplet Digital PCR Reveal Low-Level Parental FOXF1 Somatic Mosaicism in Families with Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins.

Autor:	Karolak JA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas; Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland., Liu Q; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas., Xie NG; Department of Bioengineering, Rice University, Houston, Texas., Wu LR; Department of Bioengineering, Rice University, Houston, Texas., Rocha G; Department of Neonatology, Centro Hospitalar Universitário de São João, Porto, Portugal., Fernandes S; Department of Genetics, Faculty of Medicine, Porto University, Porto, Portugal; Institute of Research and Innovation in Health, Porto, Portugal., Ho-Ming L; Clinical Genetic Service, Department of Health, Hong Kong Special Administrative Region, People's Republic of China., Lo IF; Clinical Genetic Service, Department of Health, Hong Kong Special Administrative Region, People's Republic of China., Mowat D; Centre for Clinical Genetics, Sydney Children's Hospital, Randwick Sydney, New South Wales, Australia; School of Women's and Children's Health, The University of New South Wales, Sydney, New South Wales, Australia., Fiorino EK; Division of Pediatric Pulmonary Medicine, Cohen Children's Medical Center-Northwell Health, New Hyde Park, New York., Edelman M; Division of Pediatric Pathology, Cohen Children's Medical Center-Northwell Health, New Hyde Park, New York., Fox J; Division of Medical Genetics, Cohen Children's Medical Center-Northwell Health, New Hyde Park, New York., Hayes DA; Division of Pediatric Cardiology, Cohen Children's Medical Center-Northwell Health, New Hyde Park, New York., Witte D; Divisions of Pathology, Cincinnati, Ohio., Parrott A; Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., Popek E; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas., Szafranski P; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas., Zhang DY; Department of Bioengineering, Rice University, Houston, Texas. Electronic address: dyz1@rice.edu., Stankiewicz P; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas. Electronic address: pawels@bcm.edu.
Jazyk:	angličtina
Zdroj:	The Journal of molecular diagnostics : JMD [J Mol Diagn] 2020 Apr; Vol. 22 (4), pp. 447-456. Date of Electronic Publication: 2020 Feb 07.
DOI:	10.1016/j.jmoldx.2019.12.007
Abstrakt:	Detection of low-level somatic mosaicism [alternate allele fraction (AAF) ≤ 10%] in parents of affected individuals with the apparent de novo pathogenic variants enables more accurate estimate of recurrence risk. To date, only a few systematic analyses of low-level parental somatic mosaicism have been performed. Herein, highly sensitive blocker displacement amplification, droplet digital PCR, quantitative PCR, long-range PCR, and array comparative genomic hybridization were applied in families with alveolar capillary dysplasia with misalignment of pulmonary veins. We screened 18 unrelated families with the FOXF1 variant previously determined to be apparent de novo (n = 14), of unknown parental origin (n = 1), or inherited from a parent suspected to be somatic and/or germline mosaic (n = 3). We identified four (22%) families with FOXF1 parental somatic mosaic single-nucleotide variants (n = 3) and copy number variant deletion (n = 1) detected in parental blood samples and an AAF ranging between 0.03% and 19%. In one family, mosaic allele ratio in tissues originating from three germ layers ranged between <0.03% and 0.65%. Because the ratio of parental somatic mosaicism have significant implications for the recurrence risk, this study further implies the importance of a systematic screening of parental samples for low-level and very-low-level (AAF ≤ 1%) somatic mosaicism using methods that are more sensitive than those routinely applied in diagnostics. (Copyright © 2020 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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