Abstract
Many parents with a disabled child caused by a genetic condition appreciate the option of prenatal genetic diagnosis to understand the chance of recurrence in a future pregnancy. Genome-wide tests, such as chromosomal microarray analysis and whole-exome sequencing, have been increasingly used for prenatal diagnosis, but prenatal counseling can be challenging due to the complexity of genomic data. This situation is further complicated by incidental findings of additional genetic variations in subsequent pregnancies. Here, we report the prenatal identification of a baby with a MECP2 missense variant and 15q11.2 microduplication in a family that has had a child with developmental and epileptic encephalopathy caused by a de novo KCNQ2 variant. An extended segregation analysis including extended relatives, in addition to the parents, was carried out to provide further information for genetic counseling. This case illustrates the challenges of prenatal counseling and highlights the need to understand the clinical and ethical implications of genome-wide tests.
Highlights
Having a child with disabilities caused by genetic variations can be a traumatic experience for any family
whole-exome sequencing (WES) for the fetus excluded the existence of the KCNQ2 missense variant (c.636C>G:p.D212E) but incidentally identified a missense variant in MECP2 gene (Figure 4)
The MECP2 variant is a rare variant with a minor allele frequency of 0.03%–0.05% in the East Asian population and has not been reported in the ClinVar database
Summary
Having a child with disabilities caused by genetic variations can be a traumatic experience for any family. Parents of affected children often face substantial stress with intense feelings of anxiety, fear, and depression. They often seek counseling to understand the chance of recurrence of the genetic condition in a future pregnancy (Hall et al, 2012; van Warmerdam et al, 2019; Baenziger et al, 2020). Genome-wide tests, such as whole-exome sequencing (WES) and chromosomal microarray analysis (CMA), which includes a more detailed analysis of the human genome, have gradually become more popular in the setting of prenatal diagnosis (Chang et al, 2020; Chen et al, 2020). WES provides comprehensive detection of variants in the exonic regions of genes of a genome compared with an Family With Multiple Genetic Variations analysis of a selective few genes. CMA allows rapid detection of unbalanced chromosomal anomalies, such as microdeletions and duplications, and identifies genes responsible for the phenotypes of copy number variants (CNVs) (Ceylan et al, 2018)
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