A novel FLNC frameshift and an OBSCN variant in a family with distal muscular dystrophy.
A novel FLNC c.5161delG (p.Gly1722ValfsTer61) mutation was identified in two members of a French family affected by distal myopathy and in one healthy relative. This FLNC c.5161delG mutation is one nucleotide away from a previously reported FLNC mutation (c.5160delC) that was identified in patients...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0186642 |
| _version_ | 1798032696793890816 |
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| author | Daniela Rossi Johanna Palmio Anni Evilä Lucia Galli Virginia Barone Tracy A Caldwell Rachel A Policke Esraa Aldkheil Christopher E Berndsen Nathan T Wright Edoardo Malfatti Guy Brochier Enrico Pierantozzi Albena Jordanova Velina Guergueltcheva Norma Beatriz Romero Peter Hackman Bruno Eymard Bjarne Udd Vincenzo Sorrentino |
| author_facet | Daniela Rossi Johanna Palmio Anni Evilä Lucia Galli Virginia Barone Tracy A Caldwell Rachel A Policke Esraa Aldkheil Christopher E Berndsen Nathan T Wright Edoardo Malfatti Guy Brochier Enrico Pierantozzi Albena Jordanova Velina Guergueltcheva Norma Beatriz Romero Peter Hackman Bruno Eymard Bjarne Udd Vincenzo Sorrentino |
| author_sort | Daniela Rossi |
| collection | DOAJ |
| description | A novel FLNC c.5161delG (p.Gly1722ValfsTer61) mutation was identified in two members of a French family affected by distal myopathy and in one healthy relative. This FLNC c.5161delG mutation is one nucleotide away from a previously reported FLNC mutation (c.5160delC) that was identified in patients and in asymptomatic carriers of three Bulgarian families with distal muscular dystrophy, indicating a low penetrance of the FLNC frameshift mutations. Given these similarities, we believe that the two FLNC mutations alone can be causative of distal myopathy without full penetrance. Moreover, comparative analysis of the clinical manifestations indicates that patients of the French family show an earlier onset and a complete segregation of the disease. As a possible explanation of this, the two French patients also carry a OBSCN c.13330C>T (p.Arg4444Trp) mutation. The p.Arg4444Trp variant is localized within the OBSCN Ig59 domain that, together with Ig58, binds to the ZIg9/ZIg10 domains of titin at Z-disks. Structural and functional studies indicate that this OBSCN p.Arg4444Trp mutation decreases titin binding by ~15-fold. On this line, we suggest that the combination of the OBSCN p.Arg4444Trp variant and of the FLNC c.5161delG mutation, can cooperatively affect myofibril stability and increase the penetrance of muscular dystrophy in the French family. |
| first_indexed | 2024-04-11T20:17:49Z |
| format | Article |
| id | doaj.art-4f6a22f949c9438a89e5b809cc20de57 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T20:17:49Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4f6a22f949c9438a89e5b809cc20de572022-12-22T04:04:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011210e018664210.1371/journal.pone.0186642A novel FLNC frameshift and an OBSCN variant in a family with distal muscular dystrophy.Daniela RossiJohanna PalmioAnni EviläLucia GalliVirginia BaroneTracy A CaldwellRachel A PolickeEsraa AldkheilChristopher E BerndsenNathan T WrightEdoardo MalfattiGuy BrochierEnrico PierantozziAlbena JordanovaVelina GuergueltchevaNorma Beatriz RomeroPeter HackmanBruno EymardBjarne UddVincenzo SorrentinoA novel FLNC c.5161delG (p.Gly1722ValfsTer61) mutation was identified in two members of a French family affected by distal myopathy and in one healthy relative. This FLNC c.5161delG mutation is one nucleotide away from a previously reported FLNC mutation (c.5160delC) that was identified in patients and in asymptomatic carriers of three Bulgarian families with distal muscular dystrophy, indicating a low penetrance of the FLNC frameshift mutations. Given these similarities, we believe that the two FLNC mutations alone can be causative of distal myopathy without full penetrance. Moreover, comparative analysis of the clinical manifestations indicates that patients of the French family show an earlier onset and a complete segregation of the disease. As a possible explanation of this, the two French patients also carry a OBSCN c.13330C>T (p.Arg4444Trp) mutation. The p.Arg4444Trp variant is localized within the OBSCN Ig59 domain that, together with Ig58, binds to the ZIg9/ZIg10 domains of titin at Z-disks. Structural and functional studies indicate that this OBSCN p.Arg4444Trp mutation decreases titin binding by ~15-fold. On this line, we suggest that the combination of the OBSCN p.Arg4444Trp variant and of the FLNC c.5161delG mutation, can cooperatively affect myofibril stability and increase the penetrance of muscular dystrophy in the French family.https://doi.org/10.1371/journal.pone.0186642 |
| spellingShingle | Daniela Rossi Johanna Palmio Anni Evilä Lucia Galli Virginia Barone Tracy A Caldwell Rachel A Policke Esraa Aldkheil Christopher E Berndsen Nathan T Wright Edoardo Malfatti Guy Brochier Enrico Pierantozzi Albena Jordanova Velina Guergueltcheva Norma Beatriz Romero Peter Hackman Bruno Eymard Bjarne Udd Vincenzo Sorrentino A novel FLNC frameshift and an OBSCN variant in a family with distal muscular dystrophy. PLoS ONE |
| title | A novel FLNC frameshift and an OBSCN variant in a family with distal muscular dystrophy. |
| title_full | A novel FLNC frameshift and an OBSCN variant in a family with distal muscular dystrophy. |
| title_fullStr | A novel FLNC frameshift and an OBSCN variant in a family with distal muscular dystrophy. |
| title_full_unstemmed | A novel FLNC frameshift and an OBSCN variant in a family with distal muscular dystrophy. |
| title_short | A novel FLNC frameshift and an OBSCN variant in a family with distal muscular dystrophy. |
| title_sort | novel flnc frameshift and an obscn variant in a family with distal muscular dystrophy |
| url | https://doi.org/10.1371/journal.pone.0186642 |
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