Article (Scientific journals)
X-linked dominant Charcot-Marie-Tooth neuropathy: clinical, electrophysiological, and morphological phenotype in four families with different connexin32 mutations(1).
Senderek, J.; Hermanns, B.; Bergmann, C. et al.
1999In Journal of the Neurological Sciences, 167 (2), p. 90-101
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Keywords :
Adolescent; Adult; Biopsy; Charcot-Marie-Tooth Disease/genetics/pathology; Child; Chromosome Segregation; Connexins/genetics; Evoked Potentials, Auditory, Brain Stem/physiology; Female; Genes, Dominant; Genetic Linkage; Humans; Male; Middle Aged; Mutation; Pedigree; Phenotype; Sequence Analysis, DNA; X Chromosome
Abstract :
[en] The sensorimotor neuropathy of the Charcot-Marie-Tooth type (CMT) is the most common hereditary disorder of the peripheral nervous system. The X-linked dominant form of CMT (CMTX) is associated with mutations in the gene for the gap junction protein connexin32. We examined four CMTX pedigrees two of which had potentially novel mutations in the only coding exon of connexin32. One previously unreported missense mutation, Ala39Val, was found in a family displaying a CMT phenotype with additional upper limb postural tremor reminiscent of a Roussy-Levy syndrome. A novel single base insertion, 679insT, is among the first mutations found in the fourth transmembrane domain of connexin32. Frameshift and premature stop of translation are supposed to result in a non-functional carboxy-terminus. Two further families had the known missense mutations Arg15Trp and Arg22Gln. Several female carriers were found normal on clinical presentation, however, the genotype was paralleled by decreased nerve conduction velocities (NCV) and slowed central conduction of brain stem auditory evoked responses (BAER). Median motor NCVs showed mild (in women) to intermediate (in males) reduction, indicating a peripheral neuropathy with a predominating axonal component. Nerve biopsy findings were consistent with the electrophysiological data showing a marked loss of large myelinated fibres and clusters of regenerating axons. Electron microscopy revealed various alterations of the axoglial attachment zone. This suggests defective axon-Schwann cell interactions which may induce the axonopathy in CMTX.
Disciplines :
Neurology
Pediatrics
Author, co-author :
Senderek, J.;  Institut f u¨r Neuropathologie, Universita¨tsklinikum der Rheinisch-Westf a¨lischen Technischen Hochschule, Pauwelsstraße 30, D-52074 Aachen
Hermanns, B.;  Institut f u¨r Neuropathologie, Universita¨tsklinikum der Rheinisch-Westf a¨lischen Technischen Hochschule, Pauwelsstraße 30, D-52074 Aachen
Bergmann, C.;  Institut f u¨r Neuropathologie, Universita¨tsklinikum der Rheinisch-Westf a¨lischen Technischen Hochschule, Pauwelsstraße 30, D-52074 Aachen
Boroojerdi, B.;  Neurologische Klinik, Universita¨tsklinikum der Rheinisch-Westf a¨lischen Technischen Hochschule, Aachen, Germany
Bajbouj, M.;  Klinik f u¨r Neurologie der Universita¨t Witten/Herdecke, Klinikum Wuppertal, Wuppertal, Germany
Hungs, M.;  Neurologische Klinik, Universita¨tsklinikum der Rheinisch-Westf a¨lischen Technischen Hochschule, Aachen, Germany
RAMAEKERS, Vincent ;  Kinderklinik, Universita¨tsklinikum der Rheinisch-Westf a¨lischen Technischen Hochschule, Aachen, Germany
Quasthoff, S.;  Neurologische Klinik der Technischen Universita¨t, Klinikum rechts der Isar, Mu¨nchen, Germany
Karch, D.;  Klinik f u¨r Kinderneurologie und Sozialpa¨diatrie – Kinderzentrum Maulbronn, Maulbronn, Germany
Schroder, J. M.;  Institut f u¨r Neuropathologie, Universita¨tsklinikum der Rheinisch-Westf a¨lischen Technischen Hochschule, Pauwelsstraße 30, D-52074 Aachen
Language :
English
Title :
X-linked dominant Charcot-Marie-Tooth neuropathy: clinical, electrophysiological, and morphological phenotype in four families with different connexin32 mutations(1).
Publication date :
15 August 1999
Journal title :
Journal of the Neurological Sciences
ISSN :
0022-510X
Publisher :
Elsevier, Netherlands
Volume :
167
Issue :
2
Pages :
90-101
Peer reviewed :
Peer Reviewed verified by ORBi
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