Rare among Rare: Phenotypes of Uncommon CMT Genotypes
(1) Background: Charcot–Marie–Tooth disease (CMT) is the most frequent form of inherited chronic motor and sensory polyneuropathy. Over 100 CMT causative genes have been identified. Previous reports found <i>PMP22</i>, <i>GJB1</i>, <i>MPZ</i>, and <i>MFN2<...
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MDPI AG
2021-12-01
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| author | Luca Gentile Massimo Russo Federica Taioli Moreno Ferrarini M’Hammed Aguennouz Carmelo Rodolico Antonio Toscano Gian Maria Fabrizi Anna Mazzeo |
| author_facet | Luca Gentile Massimo Russo Federica Taioli Moreno Ferrarini M’Hammed Aguennouz Carmelo Rodolico Antonio Toscano Gian Maria Fabrizi Anna Mazzeo |
| author_sort | Luca Gentile |
| collection | DOAJ |
| description | (1) Background: Charcot–Marie–Tooth disease (CMT) is the most frequent form of inherited chronic motor and sensory polyneuropathy. Over 100 CMT causative genes have been identified. Previous reports found <i>PMP22</i>, <i>GJB1</i>, <i>MPZ</i>, and <i>MFN2</i> as the most frequently involved genes. Other genes, such as <i>BSCL2</i>, <i>MORC2</i>, <i>HINT1</i>, <i>LITAF</i>, <i>GARS</i>, and autosomal dominant <i>GDAP1</i> are responsible for only a minority of CMT cases. (2) Methods: we present here our records of CMT patients harboring a mutation in one of these rare genes (<i>BSCL2</i>, <i>MORC2</i>, <i>HINT1</i>, <i>LITAF</i>, <i>GARS</i>, autosomal dominant <i>GDAP1</i>). We studied 17 patients from 8 unrelated families. All subjects underwent neurologic evaluation and genetic testing by next-generation sequencing on an Ion Torrent PGM (Thermo Fischer) with a 44-gene custom panel. (3) Results: the following variants were found: <i>BSCL2</i> c.263A > G p.Asn88Ser (eight subjects), <i>MORC2</i> c.1503A > T p.Gln501His (one subject), <i>HINT1</i> c.110G > C p.Arg37Pro (one subject), <i>LITAF</i> c.404C > G p.Pro135Arg (two subjects), <i>GARS</i> c.1660G > A p.Asp554Asn (three subjects), <i>GDAP1</i> c.374G > A p.Arg125Gln (two subjects). (4) Expanding the spectrum of CMT phenotypes is of high relevance, especially for less common variants that have a higher risk of remaining undiagnosed. The necessity of reaching a genetic definition for most patients is great, potentially making them eligible for future experimentations. |
| first_indexed | 2024-03-10T04:32:47Z |
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| last_indexed | 2024-03-10T04:32:47Z |
| publishDate | 2021-12-01 |
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| spelling | doaj.art-65bf89a6894048aab6cc93efbce57b022023-11-23T04:02:07ZengMDPI AGBrain Sciences2076-34252021-12-011112161610.3390/brainsci11121616Rare among Rare: Phenotypes of Uncommon CMT GenotypesLuca Gentile0Massimo Russo1Federica Taioli2Moreno Ferrarini3M’Hammed Aguennouz4Carmelo Rodolico5Antonio Toscano6Gian Maria Fabrizi7Anna Mazzeo8Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyDepartment of Neurological Sciences, Biomedicine and Movement Sciences, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, ItalyDepartment of Neurological Sciences, Biomedicine and Movement Sciences, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyDepartment of Neurological Sciences, Biomedicine and Movement Sciences, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy(1) Background: Charcot–Marie–Tooth disease (CMT) is the most frequent form of inherited chronic motor and sensory polyneuropathy. Over 100 CMT causative genes have been identified. Previous reports found <i>PMP22</i>, <i>GJB1</i>, <i>MPZ</i>, and <i>MFN2</i> as the most frequently involved genes. Other genes, such as <i>BSCL2</i>, <i>MORC2</i>, <i>HINT1</i>, <i>LITAF</i>, <i>GARS</i>, and autosomal dominant <i>GDAP1</i> are responsible for only a minority of CMT cases. (2) Methods: we present here our records of CMT patients harboring a mutation in one of these rare genes (<i>BSCL2</i>, <i>MORC2</i>, <i>HINT1</i>, <i>LITAF</i>, <i>GARS</i>, autosomal dominant <i>GDAP1</i>). We studied 17 patients from 8 unrelated families. All subjects underwent neurologic evaluation and genetic testing by next-generation sequencing on an Ion Torrent PGM (Thermo Fischer) with a 44-gene custom panel. (3) Results: the following variants were found: <i>BSCL2</i> c.263A > G p.Asn88Ser (eight subjects), <i>MORC2</i> c.1503A > T p.Gln501His (one subject), <i>HINT1</i> c.110G > C p.Arg37Pro (one subject), <i>LITAF</i> c.404C > G p.Pro135Arg (two subjects), <i>GARS</i> c.1660G > A p.Asp554Asn (three subjects), <i>GDAP1</i> c.374G > A p.Arg125Gln (two subjects). (4) Expanding the spectrum of CMT phenotypes is of high relevance, especially for less common variants that have a higher risk of remaining undiagnosed. The necessity of reaching a genetic definition for most patients is great, potentially making them eligible for future experimentations.https://www.mdpi.com/2076-3425/11/12/1616CMTrare genesgenotype/phenotype |
| spellingShingle | Luca Gentile Massimo Russo Federica Taioli Moreno Ferrarini M’Hammed Aguennouz Carmelo Rodolico Antonio Toscano Gian Maria Fabrizi Anna Mazzeo Rare among Rare: Phenotypes of Uncommon CMT Genotypes Brain Sciences CMT rare genes genotype/phenotype |
| title | Rare among Rare: Phenotypes of Uncommon CMT Genotypes |
| title_full | Rare among Rare: Phenotypes of Uncommon CMT Genotypes |
| title_fullStr | Rare among Rare: Phenotypes of Uncommon CMT Genotypes |
| title_full_unstemmed | Rare among Rare: Phenotypes of Uncommon CMT Genotypes |
| title_short | Rare among Rare: Phenotypes of Uncommon CMT Genotypes |
| title_sort | rare among rare phenotypes of uncommon cmt genotypes |
| topic | CMT rare genes genotype/phenotype |
| url | https://www.mdpi.com/2076-3425/11/12/1616 |
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