Gonosomal Mosaicism for a Novel <i>COL5A1</i> 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 <i>COL5A1</i> or <i>COL5A2</i> genes. Mo...
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MDPI AG
2021-11-01
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| author | Lucia Micale Thomas Foiadelli Federica Russo Luigia Cinque Francesco Bassanese Matteo Granatiero Carmela Fusco Salvatore Savasta Marco Castori |
| author_facet | Lucia Micale Thomas Foiadelli Federica Russo Luigia Cinque Francesco Bassanese Matteo Granatiero Carmela Fusco Salvatore Savasta Marco Castori |
| author_sort | Lucia Micale |
| collection | DOAJ |
| description | (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 <i>COL5A1</i> or <i>COL5A2</i> 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 <i>COL5A1</i> 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 <i>COL5A1</i> 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 <i>COL5A1</i> 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 <i>COL5A1</i>. Parental mosaicism could be an issue in cEDS and, therefore, considered for appropriate genetic counseling. |
| first_indexed | 2024-03-10T04:02:53Z |
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| last_indexed | 2024-03-10T04:02:53Z |
| publishDate | 2021-11-01 |
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| series | Genes |
| spelling | doaj.art-e273e919a4334577af4a97fb1975603f2023-11-23T08:30:30ZengMDPI AGGenes2073-44252021-11-011212192810.3390/genes12121928Gonosomal Mosaicism for a Novel <i>COL5A1</i> Pathogenic Variant in Classic Ehlers-Danlos SyndromeLucia Micale0Thomas Foiadelli1Federica Russo2Luigia Cinque3Francesco Bassanese4Matteo Granatiero5Carmela Fusco6Salvatore Savasta7Marco Castori8Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 Foggia, ItalyPediatric Clinic, IRCCS Policlinico San Matteo Foundation, University of Pavia, 27100 Pavia, ItalyDivision of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 Foggia, ItalyDivision of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 Foggia, ItalyPediatric Clinic, IRCCS Policlinico San Matteo Foundation, University of Pavia, 27100 Pavia, ItalyDivision of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 Foggia, ItalyDivision of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 Foggia, ItalyPediatric Clinic, IRCCS Policlinico San Matteo Foundation, University of Pavia, 27100 Pavia, ItalyDivision of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 Foggia, Italy(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 <i>COL5A1</i> or <i>COL5A2</i> 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 <i>COL5A1</i> 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 <i>COL5A1</i> 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 <i>COL5A1</i> 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 <i>COL5A1</i>. Parental mosaicism could be an issue in cEDS and, therefore, considered for appropriate genetic counseling.https://www.mdpi.com/2073-4425/12/12/1928classic Ehlers-Danlos syndrome<i>COL5A1</i>mosaicism |
| spellingShingle | Lucia Micale Thomas Foiadelli Federica Russo Luigia Cinque Francesco Bassanese Matteo Granatiero Carmela Fusco Salvatore Savasta Marco Castori Gonosomal Mosaicism for a Novel <i>COL5A1</i> Pathogenic Variant in Classic Ehlers-Danlos Syndrome Genes classic Ehlers-Danlos syndrome <i>COL5A1</i> mosaicism |
| title | Gonosomal Mosaicism for a Novel <i>COL5A1</i> Pathogenic Variant in Classic Ehlers-Danlos Syndrome |
| title_full | Gonosomal Mosaicism for a Novel <i>COL5A1</i> Pathogenic Variant in Classic Ehlers-Danlos Syndrome |
| title_fullStr | Gonosomal Mosaicism for a Novel <i>COL5A1</i> Pathogenic Variant in Classic Ehlers-Danlos Syndrome |
| title_full_unstemmed | Gonosomal Mosaicism for a Novel <i>COL5A1</i> Pathogenic Variant in Classic Ehlers-Danlos Syndrome |
| title_short | Gonosomal Mosaicism for a Novel <i>COL5A1</i> Pathogenic Variant in Classic Ehlers-Danlos Syndrome |
| title_sort | gonosomal mosaicism for a novel i col5a1 i pathogenic variant in classic ehlers danlos syndrome |
| topic | classic Ehlers-Danlos syndrome <i>COL5A1</i> mosaicism |
| url | https://www.mdpi.com/2073-4425/12/12/1928 |
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