Case report: The power of NGS-based CNV analysis within an exome
Apr 04, 2019

When should you choose Whole Exome Plus testing which includes the analysis of exon level and larger deletions and duplications (del/dups)?

The answer is always. In approximately 11% of the diagnostic whole exome sequencing cases we’ve interpreted, the pathogenic variant was a del/dup event. If the analysis of del/dups is omitted during the diagnostic process, there is a higher likelihood that the genetic diagnosis will remain unknown

Patient information

A young adult presented as an infant with feeding difficulties, growth retardation, recurrent infections, dysmorphic features and multiple congenital anomalies including bilateral coloboma and bilateral choanal atresia.

Previous genetic testing

Previous testing performed at another laboratory, including sequencing and MLPA of CDH7 and a chromosomal microarray, were negative.

Genetic testing at Blueprint Genetics

A Whole Exome Family Plus Test, including sequencing and CNV analysis for the proband and unaffected parents, was requested.

> Whole Exome Family Plus 

Diagnostic summary

The patient was identified to have a heterozygous de novo, likely pathogenic 3.4kb deletion in the SMC1A gene; c.(2973+1_3286-1)del, encompassing exons 20-21. SMC1A variants are known to cause a phenotype resembling Cornelia de Lange syndrome (CdLS).

Diagnostic implications

As the SMC1A deletion was not identified in either parent, the risk for the patient’s siblings to have a similarly affected child is low.

Blueprint Genetics’ Take Home

WES with high quality CNV analysis was able to detect a 2 exon deletion in this patient despite the fact that the patient had a previous normal CMA. A normal CMA does not rule out the possibility of deletions or duplications in your patient.

Read the full case report.


Last modified: October 29, 2020