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Review
. 2017 Mar;6(1):42-50.
doi: 10.1055/s-0036-1584306. Epub 2016 May 30.

Chromosomal Microarrays: Understanding Genetics of Neurodevelopmental Disorders and Congenital Anomalies

Jill A Rosenfeld  1 , Ankita Patel  1
Affiliations
Review

Chromosomal Microarrays: Understanding Genetics of Neurodevelopmental Disorders and Congenital Anomalies

Jill A Rosenfeld et al. J Pediatr Genet. 2017 Mar.

Abstract

Chromosomal microarray (CMA) testing, used to identify DNA copy number variations (CNVs), has helped advance knowledge about genetics of human neurodevelopmental disease and congenital anomalies. It has aided in discovering new CNV syndromes and uncovering disease genes. It has discovered CNVs that are not fully penetrant and/or cause a spectrum of phenotypes, including intellectual disability, autism, schizophrenia, and dysmorphisms. Such CNVs can pose challenges to genetic counseling. They also have helped increase knowledge of genetic risk factors for neurodevelopmental disease and raised awareness of possible shared etiologies among these variable phenotypes. Advances in CMA technology allow CNV identification at increasingly finer scales, improving detection of pathogenic changes, although these sometimes are difficult to distinguish from normal population variation. This paper confronts some of the challenges uncovered by CMA testing while reviewing advances in genetics and the clinical use of this test that has replaced standard karyotyping in most genetic evaluations.

Keywords: aCGH; copy number variation; microarray; microdeletion; microduplication; molecular cytogenetics.

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Figures

Fig. 1
Fig. 1
Identification of overlapping copy number variations in individuals with a shared syndrome is used to identify a critical region for a microdeletion syndrome. The shortest region of overlap of the described deletions defines the minimally deleted region required for manifestation of that syndrome.
Fig. 2
Fig. 2
Exon-targeted chromosomal microarray allows detection of clinically significant single-exon copy number variations. Genome-wide ( A ) and zoomed-in view ( B ) of aCGH results from a patient found to have a minimally sized 29kb loss in 2q23.1 within MBD5, affecting a single exon of the gene. Values along the y-axis represent the log 2 ratio of patient:control signal intensity, with circled probes indicating a deletion. Values along the x-axis represent the genomic location of the probes, with the most proximal 2q23.1 probes to the left and the most distal 2q23.1 probes to the right ( B ). Solid vertical lines represent the minimal size of the deletion, and dashed vertical lines represent the maximal size of the deletion. Vertical line along the RefSeq gene line indicates the location of exon 3 of MBD5 .
See this image and copyright information in PMC

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