Gonosomal Mosaicism for a Novel Pathogenic Variant in Classic Ehlers-Danlos Syndrome.

(1) Background: Classic Ehlers-Danlos syndrome (cEDS) is a heritable connective tissue disorder characterized by joint hypermobility and skin hyperextensibility with atrophic scarring. Many cEDS individuals carry variants in either the or genes. Mosaicism is relatively common in heritable connective tissue disorders but is rare in EDS. In cEDS, a single example of presumed gonosomal mosaicism for a variant has been published to date. (2) Methods: An 8-year-old girl with cEDS was analyzed by next-generation sequencing (NGS). Segregation was performed by Sanger sequencing in her unaffected parents. In the father, the mosaicism of the variant was further analyzed by targeted NGS and droplet digital PCR (ddPCR) in the blood and by Sanger sequencing in other tissues. (3) Results: The NGS analysis revealed the novel germline heterozygous c.1369G>T, p.(Glu457*) variant in the proband. Sanger chromatogram of the father's blood specimen suggested the presence of a low-level mosaicism for the variant, which was confirmed by NGS and estimated to be 4.8% by ddPCR. The mosaicism was also confirmed by Sanger sequencing in the father's saliva, hair bulbs and nails. (4) Conclusions: We described the second case of cEDS caused by paternal gonosomal mosaicism in . Parental mosaicism could be an issue in cEDS and, therefore, considered for appropriate genetic counseling.