Lessons Learned from CNV Analysis of Major Birth Defects

• Published in: International journal of molecular sciences Vol. 21; no. 21; p. 8247
• Main Authors: Hilger, Alina Christine, Dworschak, Gabriel Clemens, Reutter, Heiko Martin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 03.11.2020; MDPI AG
• Subjects: birth defect; Child; CNV; Congenital Abnormalities - epidemiology; Congenital Abnormalities - genetics; copy number variation; de novo; DNA Copy Number Variations - genetics; DNA Mutational Analysis - methods; embryonic development; Female; Humans; Infant, Newborn; Intellectual Disability - epidemiology; Intellectual Disability - genetics; Karyotyping - methods; Male; Nervous System Malformations - epidemiology; Nervous System Malformations - genetics; Phenotype; Polymorphism, Genetic - physiology; Pregnancy; Review; birth defect; CNV; copy number variation; de novo; embryonic development
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21218247

The treatment of major birth defects are key concerns for child health. Hitherto, for the majority of birth defects, the underlying cause remains unknown, likely to be heterogeneous. The implicated mortality and/or reduced fecundity in major birth defects suggest a significant fraction of mutational de novo events among the affected individuals. With the advent of systematic array-based molecular karyotyping, larger cohorts of affected individuals have been screened over the past decade. This review discusses the identification of disease-causing copy-number variations (CNVs) among individuals with different congenital malformations. It highlights the differences in findings depending on the respective congenital malformation. It looks at the differences in findings of CNV analysis in non-isolated complex congenital malformations, associated with central nervous system malformations or intellectual disabilities, compared to isolated single organ-system malformations. We propose that the more complex an organ system is, and the more genes involved during embryonic development, the more likely it is that mutational de novo events, comprising CNVs, will confer to the expression of birth defects of this organ system.