Artikel
Inverted formin 2-related Charcot-Marie-Tooth disease: extension of the mutational spectrum and pathological findings in Schwann cells and axons
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Autoren
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Andreas Roos
- Leibniz-Institut für Analytische Wissenschaften – ISAS, Tissue Omics, Dortmund, Germany
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Joachim Weis
- Leibniz-Institut für Analytische Wissenschaften – ISAS, Tissue Omics, Dortmund, Germany; Institute of Neuropathology, RWTH Aachen University Hospital, Aachen, Germany
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Rudolf Korinthenberg
- Leibniz-Institut für Analytische Wissenschaften – ISAS, Tissue Omics, Dortmund, Germany; Institute of Neuropathology, RWTH Aachen University Hospital, Aachen, Germany; Medical Center for Neuropaediatrics and Muscle Diseases, University Hospital Freiburg, Freiburg, Germany
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Michaela Auer-Grumbach
- Leibniz-Institut für Analytische Wissenschaften – ISAS, Tissue Omics, Dortmund, Germany; Institute of Neuropathology, RWTH Aachen University Hospital, Aachen, Germany; Medical Center for Neuropaediatrics and Muscle Diseases, University Hospital Freiburg, Freiburg, Germany; Department of Orthopaedics, Medical Univesity Vienna, Vienna, Austria
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Jan Senderek
- Leibniz-Institut für Analytische Wissenschaften – ISAS, Tissue Omics, Dortmund, Germany; Institute of Neuropathology, RWTH Aachen University Hospital, Aachen, Germany; Medical Center for Neuropaediatrics and Muscle Diseases, University Hospital Freiburg, Freiburg, Germany; Department of Orthopaedics, Medical Univesity Vienna, Vienna, Austria; Friedrich-Baur Institute, Ludwig-Maximilians University of Munich, Department of Neurology, Munich, Germany
| Veröffentlicht: | 25. August 2015 |
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Gliederung
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Question: Mutations in the gene encoding inverted formin FH2 and WH2 domain containing protein (INF2), a Cdc42 effector involved in the regulation of actin dynamics, cause focal segmental glomerulosclerosis (FSGS) and intermediate Charcot-Marie-Tooth neuropathy combined with FSGS (FSGS-CMT). Here, we report on our clinical, morphological and genetic findings in six patients from four families with sensorimotor polyneuropathy and FSGS.
Methods and results: Molecular genetic testing of INF2 in the six patients revealed two known and two novel missense mutations in the second and fourth exon of the gene. Nerve conduction velocities of the patients were moderately slowed and amplitudes of sensory and motor potentials were decreased. One patient had internal hydrocephalus and was intellectually disabled. Investigations of one nerve biopsy confirmed the diagnosis of intermediate type CMT and revealed occasional abnormal in- and outfoldings of myelin sheaths and expansions of the endoplasmic reticulum in axons and Schwann cells.
Conclusion: While earlier reports suggested that mutations causing FSGS-CMT are restricted to exons 2 and 3 of the INF2 gene, we found one CMT-FSGS causing mutation (p.Glu184Lys) in exon 4 extending the critical region of INF2 for rapid CMT-FSGS molecular genetic diagnosis. Study of the nerve biopsy showed abnormalities that might be related to the known role of the INF2 binding partner CDC42 in myelination and to the ER association of INF2.
