Identification of a rare SEPT9 variant in a family with autosomal dominant Charcot-Marie-Tooth disease
Abstract Background Charcot-Marie-Tooth disease (CMT) is one of the most commonly inherited neurological disorders. A growing number of genes, involved in glial and neuronal functions, have been associated with different subtypes of CMT leading to improved diagnostics and understanding of pathophysi...
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| Online Access: | http://link.springer.com/article/10.1186/s12881-020-0984-7 |
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doaj-fcf40c8636684ab7983bc0c7c2a595812021-04-02T08:39:31ZengBMCBMC Medical Genetics1471-23502020-03-012111710.1186/s12881-020-0984-7Identification of a rare SEPT9 variant in a family with autosomal dominant Charcot-Marie-Tooth diseaseGerrit M. Grosse0Christine Bauer1Bruno Kopp2Christoph Schrader3Alma Osmanovic4Department of Neurology, Hannover Medical SchoolCenter for Genomics and Transcriptomics (CeGaT GmbH)Department of Neurology, Hannover Medical SchoolDepartment of Neurology, Hannover Medical SchoolDepartment of Neurology, Hannover Medical SchoolAbstract Background Charcot-Marie-Tooth disease (CMT) is one of the most commonly inherited neurological disorders. A growing number of genes, involved in glial and neuronal functions, have been associated with different subtypes of CMT leading to improved diagnostics and understanding of pathophysiological mechanisms. However, some patients and families remain genetically unsolved. Methods We report on a German family including four affected members over three generations with a CMT phenotype accompanied by cognitive deficits, predominantly with regard to visual abilities and episodic memory. Results A comprehensive clinical characterization followed by a sequential diagnostic approach disclosed a heterozygous rare SEPT9 missense variant c.1406 T > C, p.(Val469Ala), that segregates with disease. SEPT9 has been linked to various intracellular functions, such as cytokinesis and membrane trafficking. Interestingly, SEPT9-mutations are known to cause hereditary neuralgic amyotrophy (HNA), a recurrent focal peripheral neuropathy. Conclusion We, for the first time, present a SEPT9 variant associated to a CMT phenotype and suggest SEPT9 as new sufficient candidate gene in CMT.http://link.springer.com/article/10.1186/s12881-020-0984-7Charcot-Marie-ToothNext generation sequencingSEPT9SeptinInherited neuropathy |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Gerrit M. Grosse Christine Bauer Bruno Kopp Christoph Schrader Alma Osmanovic |
| spellingShingle |
Gerrit M. Grosse Christine Bauer Bruno Kopp Christoph Schrader Alma Osmanovic Identification of a rare SEPT9 variant in a family with autosomal dominant Charcot-Marie-Tooth disease BMC Medical Genetics Charcot-Marie-Tooth Next generation sequencing SEPT9 Septin Inherited neuropathy |
| author_facet |
Gerrit M. Grosse Christine Bauer Bruno Kopp Christoph Schrader Alma Osmanovic |
| author_sort |
Gerrit M. Grosse |
| title |
Identification of a rare SEPT9 variant in a family with autosomal dominant Charcot-Marie-Tooth disease |
| title_short |
Identification of a rare SEPT9 variant in a family with autosomal dominant Charcot-Marie-Tooth disease |
| title_full |
Identification of a rare SEPT9 variant in a family with autosomal dominant Charcot-Marie-Tooth disease |
| title_fullStr |
Identification of a rare SEPT9 variant in a family with autosomal dominant Charcot-Marie-Tooth disease |
| title_full_unstemmed |
Identification of a rare SEPT9 variant in a family with autosomal dominant Charcot-Marie-Tooth disease |
| title_sort |
identification of a rare sept9 variant in a family with autosomal dominant charcot-marie-tooth disease |
| publisher |
BMC |
| series |
BMC Medical Genetics |
| issn |
1471-2350 |
| publishDate |
2020-03-01 |
| description |
Abstract Background Charcot-Marie-Tooth disease (CMT) is one of the most commonly inherited neurological disorders. A growing number of genes, involved in glial and neuronal functions, have been associated with different subtypes of CMT leading to improved diagnostics and understanding of pathophysiological mechanisms. However, some patients and families remain genetically unsolved. Methods We report on a German family including four affected members over three generations with a CMT phenotype accompanied by cognitive deficits, predominantly with regard to visual abilities and episodic memory. Results A comprehensive clinical characterization followed by a sequential diagnostic approach disclosed a heterozygous rare SEPT9 missense variant c.1406 T > C, p.(Val469Ala), that segregates with disease. SEPT9 has been linked to various intracellular functions, such as cytokinesis and membrane trafficking. Interestingly, SEPT9-mutations are known to cause hereditary neuralgic amyotrophy (HNA), a recurrent focal peripheral neuropathy. Conclusion We, for the first time, present a SEPT9 variant associated to a CMT phenotype and suggest SEPT9 as new sufficient candidate gene in CMT. |
| topic |
Charcot-Marie-Tooth Next generation sequencing SEPT9 Septin Inherited neuropathy |
| url |
http://link.springer.com/article/10.1186/s12881-020-0984-7 |
| work_keys_str_mv |
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