Copy number alterations involving 59 ACMG-recommended secondary findings genes
Autor: | Jie Hu, Suneeta Madan-Khetarpal, Devereux N. Saller, Daniel B. Bellissimo, Mahmoud Aarabi, Damara Ortiz, Urvashi Surti, Aleksandar Rajkovic, Svetlana A. Yatsenko |
---|---|
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Adolescent DNA Copy Number Variations Genetics Medical Genomics 030105 genetics & heredity Biology Polymorphism Single Nucleotide DNA sequencing 03 medical and health sciences Young Adult Exome Sequencing Genetics medicine Humans Clinical significance Exome Copy-number variation Genetic Testing Child Gene Genetics (clinical) Microarray analysis techniques Genome Human Infant Microarray Analysis 030104 developmental biology Child Preschool Cytogenetic Analysis Medical genetics Female |
Zdroj: | Clinical geneticsREFERENCES. 98(6) |
ISSN: | 1399-0004 |
Popis: | In clinical exome/genome sequencing, the American College of Medical Genetics and Genomics (ACMG) recommends reporting of secondary findings unrelated to a patient's phenotype when pathogenic single-nucleotide variants (SNVs) are observed in one of 59 genes associated with a life-threatening, medically actionable condition. Little is known about the incidence and sensitivity of chromosomal microarray analysis (CMA) for detection of pathogenic copy number variants (CNVs) comprising medically-actionable genes. Clinical CMA has been performed on 8865 individuals referred for molecular cytogenetic testing. We retrospectively reviewed the CMA results to identify patients with CNVs comprising genes included in the 59-ACMG list of secondary findings. We evaluated the clinical significance of these CNVs in respect to pathogenicity, phenotypic manifestations, and heritability. We identified 23 patients (0.26%) with relevant CNV either deletions comprising the entire gene or intragenic alterations involving one or more secondary findings genes. A number of patients and/or their family members with pathogenic CNVs manifest or expected to develop an anticipated clinical phenotype and would benefit from preventive management similar to the patients with pathogenic SNVs. To improve patients' care standardization should apply to reporting of both sequencing and CNVs obtained via clinical genome-wide analysis, including chromosomal microarray and exome/genome sequencing. |
Databáze: | OpenAIRE |
Externí odkaz: |