Genotype-phenotype correlation in a family with late onset CMT and an MPZ lys236del mutation

Sowden, Janet E.; Logigian, Eric L.; Malik, Kamal; Herrmann, David N.

doi:10.1136/jnnp.2004.043968

Cited by 12 publications

(6 citation statements)

References 6 publications

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“…In CMT2J some carriers of Thr124Met mutation in MPZ gene exhibited Adie's pupil with no polyneuropathic signs [9,16]. In a pedigree with MPZ Lys236del mutation causing adult-onset CMT1 phenotype, one gene mutation carrier aged 15 years had normal neurologic examination except for mildly reduced vibration sense, and normal nerve electrophysiologic findings [28]. In a comprehensive study of 90 patients from one large Austrian family and two unrelated German families with BSCL2 N88S mutation, it was found that 24.4% were asymptomatic or sub-clinically affected [1,30].…”

Section: Discussionmentioning

confidence: 99%

Reduced penetrance in hereditary motor neuropathy caused by TRPV4 Arg269Cys mutation

et al. 2011

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Incomplete penetrance has rarely been reported in Charcot-Marie-Tooth disease. Our aim is to describe reduced penetrance in a hereditary motor neuropathy pedigree due to mutation in the transient receptor potential vallinoid 4 (TRPV4) gene. The pedigree comprised two affected members, the proband aged 44 years and her affected daughter aged 7 years, and seven additional related subjects, three of whom were subclinical gene mutation carriers aged 9, 40 and 70 years. Clinico-electrophysiological studies, MRI of lower-limb musculature and genetic testing of the TRPV4 were performed. The proband presented with a moderate facio-scapulo-peroneal syndrome, whereas her symptomatic daughter suffered from severe congenital spinal muscular atrophy with arthrogryposis, laryngomalacia, and vocal cord paresis. Electrophysiological evaluation revealed a pure motor axonal neuropathy. In the proband, MRI showed extensive and widespread fatty atrophy of lower-leg musculature, whereas in thigh musculature there was just mild distal fatty infiltration of vastus lateralis. Genetic testing revealed a heterozygous Arg269Cys mutation in the TPRV4 gene. In all three mutation carriers results from clinical and electrophysiological examination, and MRI of foot and lower-leg musculature were normal. We conclude that non-penetrance may be an integral feature of neuropathic syndromes associated with TRPV4 gene mutation.

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Section: Discussionmentioning

confidence: 99%

Reduced penetrance in hereditary motor neuropathy caused by TRPV4 Arg269Cys mutation

et al. 2011

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“…In a late-onset CMT family associated with MPZ K236del mutation, comprising two symptomatic and two sub-clinical heterozygous mutation carriers, median MNCV ranged from 29 to 56 m/s with normal CMAP amplitudes, and prolonged DML in two cases [108].…”

Section: Di-cmtd (Mim#607791)mentioning

confidence: 99%

“…Without knowing CMAP amplitude values, it does not seem possible to us to discard that the observed motor conduction slowing could merely be due to axonal loss (see above). In any case, three definite DI-CMT pedigrees associated with MPZ mutation have been reported [108][109][110], briefly analyzed below.…”

Section: Di-cmtd (Mim#607791)mentioning

confidence: 99%

Intermediate Charcot–Marie–Tooth disease: an electrophysiological reappraisal and systematic review

et al. 2017

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Charcot-Marie-Tooth disease (CMT) is the most frequent form of inherited neuropathy with great variety of phenotypes, inheritance patterns, and causative genes. According to median motor nerve conduction velocity (MNCV), CMT is divided into demyelinating (CMT1) with MNCV below 38 m/s, axonal (CMT2) with MNCV above 38 m/s, and intermediate CMT with MNCV between 25 and 45 m/s. In each category, transmission may be autosomal dominant, autosomal recessive, or X-linked. The nosology of intermediate CMT is controversial because of concerns about electrophysiological delimitation. A systematic computer-based literature search was conducted on PubMed, using the following MeSH: (1) intermediate Charcot-Marie-Tooth; (2) X-linked intermediate Charcot-Marie-Tooth; and (3) X-linked Charcot-Marie-Tooth and electrophysiology. We retrieved 225 articles reporting X-linked CMT or intermediate CMT with electrophysiological information. After eligibility, 156 papers were used for this review. In assessing median MNCV, compound muscle action potential (CMAP) amplitudes were taken into account. In cases with attenuated CMAP and wherever possible, proximal median MNCV was used for accurate definition of conduction slowing in the intermediate range. In the vast majority of males with X-linked CMT associated with GJB1 mutation (CMTX1), median MNCV was intermediate. CMT associated with DRP2 mutation is another well-documented X-linked intermediate disorder. Autosomal dominant intermediate CMT (DI-CMT) encompasses 11 different types; six of them with assigned phenotype MIM number and the remaining five being unnumbered. Based on available electrophysiological information, we wonder if DI-CMTA should be reclassified within CMT2. Autosomal recessive intermediate CMT (RI-CMT) covers four numbered MIM phenotypes though, in accordance with reported electrophysiology, two of them (RI-CMTB and RI-CMTD) should probably be reclassified within AR-CMT2. We conclude that intermediate CMT is a complex inherited syndrome, whose characterization requires a specific electrophysiological protocol comprising evaluation of upper limb proximal nerve trunks when distal CMAP amplitudes are reduced, and that an updated version of MIM phenotype numbering is needed.

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“…Because the defect affects all myelin in a uniform fashion, abnormal temporal dispersion and/ or conduction block is not seen, and this helps to distinguish the inherited demyelinating forms from inflammatory etiologies. A caveat of this assumption is the finding of abnormal temporal dispersion and conduction block in certain forms of CMT1 (MPZ, GJB1) 4,5 ; therefore, the absence of conduction block and abnormal temporal dispersion can be regarded as supportive of an inherited etiology, but the presence must be interpreted with caution.…”

Section: Electrophysiologic Datamentioning

confidence: 99%

Alphabet Soup: Making Sense of Genetic Testing in CMT

Lawson

Gharibshahi

2010

Semin Neurol

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The diagnosis of inherited neuropathies can be challenging in several ways. First, a hereditary neuropathy must be suspected. Although some family histories are clear with multiple members affected, other families require directed inquiry. Second, even when a hereditary neuropathy is clear, it can be difficult to make a genetic characterization. The field of genotyping is expanding so rapidly, it is difficult to know what tests to order. The authors share their guidelines for the diagnosis of inherited neuropathies.

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Genotype-phenotype correlation in a family with late onset CMT and an MPZ lys236del mutation

Cited by 12 publications

References 6 publications

Reduced penetrance in hereditary motor neuropathy caused by TRPV4 Arg269Cys mutation

Reduced penetrance in hereditary motor neuropathy caused by TRPV4 Arg269Cys mutation

Intermediate Charcot–Marie–Tooth disease: an electrophysiological reappraisal and systematic review

Alphabet Soup: Making Sense of Genetic Testing in CMT

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