PMC9554350_01
Clinical picture, pedigree of the family and sequencing results of the mother's buccal swab DNA. (A) Facial features, right hand and feet of the affected patient. (B) Face of the mosaic carrier mother. (C) Pedigree of the family showing Mendelian transmission of the SMC1A variant and the different genotypes present in mother and son: black symbol represents the affected patient with heterozygous pathogenic variant (II-1). In individual I-2, the circle in the center of the symbol indicates asymptomatic carrier, and mosaicism condition is highlighted with a black dots pattern inside. Sanger sequencing results of the targeted SMC1A variant [NM_006306.3:c.2078G>A, p. (Arg693Gln)] analyzed in blood-derived DNA of the patient and his mother are shown below their respective representative symbols. The non-affected father (I-1) is indicated as an open symbol. (D) Sanger chromatogram and Integrative Genomics Viewer (IGV) view of sequencing results of the targeted SMC1A variant (NM_006306.3:c.2078 = /G>A) in patient's mother (left) and a healthy female control (right) buccal swab-derived DNA.
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F1
The phenotype of the patient is shown in Figure 1A, that was subjected to an additional analysis with the Face2Gene application, in which CdLS was the first choice syndrome with a high gestalt level. Remarkably, the chromatogram obtained from SnapGene Viewer (Dotmatics) after Sanger sequencing of DNA from mother's peripheral blood resulted inconclusive (Figure 1C), and a more comprehensive study of a suspected mosaicism condition was done by testing another tissue sample through deeper sequencing techniques. Deep sequencing yielded a coverage of 942 reads of the targeted genomic position (Figure 1D), which allowed the detection of the variant of interest in such a low mosaic level. Sanger sequencing of the mother's buccal swab-derived DNA was also carried out, and once again, suggested a possible scenario of genetic mosaicism (Figure 1D), but could not anyway ensure so. These results were contrasted with an additional analysis of a buccal swab sample from a healthy female control, verifying that the detection of the variant with an AAF so low was accurate and did not result from intrinsic errors of the panel (Figure 1D).