The Cytoscan HD Array in the Diagnosis of Neurodevelopmental Disorders.

Francesca Scionti,Daniela Concolino,Maria Di Martino,Valentina Bruni,Licia Pensabene

doi:10.3390/ht7030028

Francesca Scionti, Daniela Concolino + Show 3 more

Open Access

https://doi.org/10.3390/ht7030028

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Journal: High-throughput	Publication Date: Sep 14, 2018
Citations: 20	License type: CC BY 4.0

Affiliation: Magna Graecia University

Abstract

Submicroscopic chromosomal copy number variations (CNVs), such as deletions and duplications, account for about 15–20% of patients affected with developmental delay, intellectual disability, multiple congenital anomalies, and autism spectrum disorder. Most of CNVs are de novo or inherited rearrangements with clinical relevance, but there are also rare inherited imbalances with unknown significance that make difficult the clinical management and genetic counselling. Chromosomal microarrays analysis (CMA) are recognized as the first-line test for CNV detection and are now routinely used in the clinical diagnostic laboratory. The recent use of CMA platforms that combine classic copy number analysis with single-nucleotide polymorphism (SNP) genotyping has increased the diagnostic yields. Here we discuss the application of the Cytoscan high-density (HD) SNP-array for the detection of CNVs. We provide an overview of molecular analyses involved in identifying pathogenic CNVs and highlight important guidelines to establish pathogenicity of CNV.

Highlights

A contribution to the human genome variability comes from copy number variations (CNVs), which involves unbalanced rearrangements, such as deletions and duplications, of intermediate size (>50 base pairs, bp)
The spectrum phenotype of CNVs varies from normal to pathogenic conditions. It is well-established that CNVs account for about 15–20% of patients affected with developmental delay (DD), intellectual disability (ID), multiple congenital anomalies (MCA), and autism spectrum disorder (ASD) [2]
Over the past 3–5 years, high-resolution chromosomal microarray analysis (CMA) platforms that combine classic copy number analysis with single-nucleotide polymorphism (SNP) genotyping have identified many small CNVs that underlie neurodevelopmental disorders leading to increases in diagnostic yield for some of these patients [6]

Summary

Introduction

A contribution to the human genome variability comes from copy number variations (CNVs), which involves unbalanced rearrangements, such as deletions and duplications, of intermediate size (>50 base pairs, bp). The spectrum phenotype of CNVs varies from normal to pathogenic conditions It is well-established that CNVs account for about 15–20% of patients affected with developmental delay (DD), intellectual disability (ID), multiple congenital anomalies (MCA), and autism spectrum disorder (ASD) [2]. These structural variants cannot be resolved by standard karyotype analysis because of its resolution limited to chromosomal aberrations greater than 3 Mb in size. Over the past 3–5 years, high-resolution CMA platforms that combine classic copy number analysis with single-nucleotide polymorphism (SNP) genotyping have identified many small CNVs that underlie neurodevelopmental disorders leading to increases in diagnostic yield for some of these patients [6]. In this review we discuss the application of Cytoscan high-density (HD) SNP-array in diagnostics providing an overview of its methodology and highlighting important guidelines to establish pathogenicity of CNV

Chromosomal Microarray Platforms

Cytoscan HD Platform

Clinical Applications of Cytoscan HD Array in Neurodevelopmental Disorders

Clinical Interpretation of Copy Number Variations

Findings

Conclusions