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Exome-first Approach Identified Novel INDELs and Gene Deletions in Mowat-Wilson Syndrome Patients

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Case Reports

Exome-first Approach Identified Novel INDELs and Gene Deletions in Mowat-Wilson Syndrome Patients

Maria Florencia Gosso et al. Hum Genome Var.

Abstract

Mowat-Wilson syndrome (MWS) is characterized by severe intellectual disability, absent or impaired speech and microcephaly, with a gradual post-natal onset. The syndrome is often confused with other Angelman-like syndromes (ALS) during infancy, but in older children and adults, the characteristic facial gestalt of Mowat-Wilson syndrome allows it to be distinguished easily from ALS. We report two cases in which an exome-first approach of patients with MWS identified two novel deletions in the ZEB2 gene ranging from a 4 base deletion (case 1) to at least a 573 Kb deletion (case 2).

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. Patient 1 exome analysis.
a The 4-bp INDEL variant of the ZEB2 gene was identified in patient 1 from WES analysis. b Schematic representation of the ZEB2 protein and its domains, indicating the location of the frameshift mutation that results in premature protein termination. c Screen capture of the BAM files analysis using the Integrative Genomics Viewer (http://software.broadinstitute.org/software/igv/bam) for the ZEB2 INDEL p.Ser726TyrfsTer7 variant that was found in patient 1 and both of their parents. The blue arrow indicates the exact location of the 4-bp INDEL leading to a frameshift that results in premature protein termination
Fig. 2
Fig. 2. Patient 2 exome analysis.
a Summary of the annotated SNVs in the ZEB2 gene that were found to be either benign or pathogenic (8ZEB2 and VUS (GTDC1)) in the patient. b A detailed diagram of the deleted region (chr2:144704611-145277958) encompassing ZEB2 as well as the neighboring GTDC1 and TEX41 genes as detected using the XHMM algorithm, which encompasses 25 target regions that are highlighted in red and are equivalent to 0.573 Mb. c The ZEB2 pathogenic deletion (1.08 Mb), as confirmed by a CGH assay (arr[GRCh37] 2q22.3(144569168_145648045)x1), which includes the 0.573 Mb deletion detected via WGS. The CGH array extended the deleted region to include a partial deletion of the downstream TEX41 gene, which is a non-protein coding gene of unknown function

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