Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D)

Ionâşescu, Victor; Searby, Charles; Sheffield, Val C.; Roklina, Tatiana; Nishimura, Darrell; Ionasescu, Rebecca

doi:10.1093/hmg/5.9.1373

Cited by 127 publications

(73 citation statements)

References 19 publications

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“…Recently, patients presenting with axonal hereditary motor and sensory neuropathy (HMSN type 2, i.e. Charcot-Marie-Tooth 2 disease or CMT2 syndrome) and predominant hand muscle involvement have been genetically subclassified as CMT2D [3,4]. The phenotype of CMT2D is thus similar to dHMN-V [4].…”

Section: Introductionmentioning

confidence: 99%

Further evidence for genetic heterogeneity of distal HMN type V, CMT2 with predominant hand involvement and Silver syndrome

Rohkamm

Reilly

Lochmüller

et al. 2007

Journal of the Neurological Sciences

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Objective-Distal hereditary motor neuropathy type V (dHMN-V) and Charcot-Marie-Tooth syndrome (CMT) type 2 presenting with predominant hand involvement, also known as CMT2D and Silver syndrome (SS) are rare phenotypically overlapping diseases which can be caused by mutations in the Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2) and in the glycyl-tRNA synthetase encoding (GARS) genes. Mutations in the heat-shock proteins HSPB1 and HSPB8 can cause related distal hereditary motor neuropathies (dHMN) and are considered candidates for dHMN-V, CMT2, and SS.Design-To define the frequency and distribution of mutations in the GARS, BSCL2, HSPB1 and HSPB8 genes we screened 33 unrelated sporadic and familial patients diagnosed as either dHMN-V, CMT2D or SS. Europe PMC Funders Author Manuscripts Europe PMC Funders Author ManuscriptsResults-Four patients diagnosed with dHMN-Vor SS carried known heterozygous BSCL2 mutations (N88S and S90L). In one dHMN-V patient we detected a putative GARS mutation (A57V). No mutations were detected in HSPB1 and HSPB8. The diagnostic yield gained in the series of 33 probands was 12% for BSCL2 mutations and 3% for GARS mutations. In the series of unclassified dHMN and complicated HSP cases no mutations were found.Conclusions-Our data confirm that most likely only two mutations (N88S, S90L) in exon 3 of BSCL2 may lead to dHMN-V or SS phenotypes. Mutations in GARS, HSPB1 and HSPB8. are not a common cause of dHMN-V, SS and CMT2D. We would therefore suggest that a genetic testing of dHMN-V and SS patients should begin with screening of exon 3 of the BSCL2 gene. Screening of the GARS gene is useful in patients with CMT2 with predominant hand involvement and dHMN-V. The rather low frequencies of BSCL2, GARS, HSPB1 and HSPB8 mutations in dHMN-V, CMT2D and SS patients strongly point to further genetic heterogeneity of these related disorders.

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Section: Introductionmentioning

confidence: 99%

Further evidence for genetic heterogeneity of distal HMN type V, CMT2 with predominant hand involvement and Silver syndrome

Rohkamm

Reilly

Lochmüller

et al. 2007

Journal of the Neurological Sciences

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“…CMT1 is the demyelinating form, characterized by motor nerve conduction velocity (MNCV) below 35 m/s, whereas CMT2 is the axonal form, characterized by normal MNCV (Dyck et al, 1993). CMT2 has been linked to 3 loci on 1p35-36, 3q13-q22 and 7p14 (Ben Othmane et al, 1993;Kwon et al, 1995;Ionasescu et al, 1996). CMT1A is mostly caused by a duplication of the PMP22 gene on chromosome 17p11.2-p12 (Timmerman et al, 1992;Valentijn et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Autonomic and respiratory dysfunction in Charcot–Marie–Tooth disease due to Thr124Met mutation in the myelin protein zero gene

Stojkovic

Seze

Dubourg³

et al. 2003

Clinical Neurophysiology

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Objective: To report the clinical and electrophysiological characteristics of a family presenting Charcot -Marie-Tooth disease (CMT) associated with autonomic nervous system disturbances.Methods: We studied nerve conduction values, postural adaptation, sympathetic skin reflex, the variation in heart rate by the Valsalva ratio and pupillometry in 7 members of a French family in which CMT due to a Thr124Met mutation in the myelin protein zero (MPZ) gene was diagnosed.Results: Clinical and laboratory evidence of autonomic nervous system disturbances were found in the affected individuals. The clinical phenotype was characterized by sensorimotor peripheral neuropathy, defined as axonal type by electrophysiological studies, and was associated with severe pain, bladder dysfunction, sudorimotor disturbances and abolished pupillary reflex to light. Moreover, two patients had severe restrictive respiratory insufficiency requiring noninvasive mechanical ventilation.Conclusions: Our study demonstrates that autonomic disturbances may be one of the major clinical signs associated with CMT secondary to MPZ gene mutation in codon 124. Testing of pupillary reflex allows the discrimination of affected and unaffected subjects in our family. However, involvement of the autonomic nervous system in this type of neuropathy is unclear and further studies are required to elucidate the role of the MPZ gene in the autonomic nervous system.

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“…5 A fourth CMT2 type (CMT2C) has not been linked to any known locus. 6 Interestingly, distinct point mutations in the myelin protein zero (MPZ) gene also may be responsible for a CMT2-like phenotype.…”

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confidence: 99%

Clinical and genetic study of a large Charcot–Marie–Tooth type 2A family from southern Italy

Muglia

Zappia²,

Timmerman³

et al. 2001

Neurology

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Article abstract-The authors report a large pedigree from southern Italy with Charcot-Marie-Tooth disease type 2A (CMT2A). The clinical picture was uniform and characterized by distal muscular weakness and atrophy in the lower limbs, reduced or absent tendon reflexes mainly in the lower limbs, and mild sensory impairment in the feet. Significant linkage to the CMT2A locus on chromosome 1p35-p36 was detected. Based on informative recombination in affected individuals, the authors mapped the CMT2A gene between D1S160 and D1S170.

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Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D)

Cited by 127 publications

References 19 publications

Further evidence for genetic heterogeneity of distal HMN type V, CMT2 with predominant hand involvement and Silver syndrome

Further evidence for genetic heterogeneity of distal HMN type V, CMT2 with predominant hand involvement and Silver syndrome

Autonomic and respiratory dysfunction in Charcot–Marie–Tooth disease due to Thr124Met mutation in the myelin protein zero gene

Clinical and genetic study of a large Charcot–Marie–Tooth type 2A family from southern Italy

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