Phenotype of Charcot–Marie–Tooth disease Type 2

Bienfait, H.M.E.; Baas, Frank; Koelman, J.H.T.M.; Haan, Rob J. de; Engelen, B.G.M. van; Gabreëls-Festen, A.A.W.M.; Visser, B.W. Ongerboer de; Meggouh, Farid; Weterman, Marian A. J.; Jonghe, Peter De; Timmerman, Vincent; Visser, Marjolein

doi:10.1212/01.wnl.0000263479.97552.94

Cited by 54 publications

(42 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Both mutations have been described previously [11][12][13]15,16]. In proband 5 we detected a heterozygous C to T substitution changing alanine to valine at codon 57 (c.688 C > T, p.A57V) in the GARS gene which is novel.…”

Section: Gene Mutation Analysissupporting

confidence: 52%

“…So far, only the two heterozygous mutations N88S and S90L in exon 3 of the BSCL2 gene have been reported in patients with dHMN [11][12][13][14][15][16]. Our study highlights these two mutations as a cause of dHMN-V.…”

Section: Discussionmentioning

confidence: 53%

“…In a number of families diagnosed as either dHMN-V or SS two heterozygous mutations (N88S, S90L) located in exon 3 in the Berardinelli-Seip congenital lipodystrophy gene (BSCL2) were identified [11]. Clinical examination of more than 90 patients with the BSCL2 N88S substitution showed that it is most often associated with a dHMN-V phenotype and less frequently, additional prominent spasticity and mild sensory disturbances are found in the lower limbs [2,[12][13][14][15]. Up to date, the S90L substitution was only described in three families and often resulted in a spastic paraplegia phenotype with marked weakness and wasting in the hands suggesting the clinical diagnosis of SS [11,15,16].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Section: Gene Mutation Analysissupporting

confidence: 52%

Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

show abstract

“…CMT is one of the most commonly inherited neurological disorders, affecting ϳ1 in 2500 people (17). CMT can be further divided into two categories; type 1 is a demyelinating neuropathy, whereas type 2 is axonal (18). CMT-2D begins only after young adulthood, and unlike other CMTs, it typically causes more severe symptoms in the hands (19).…”

mentioning

confidence: 99%

Cocrystal Structures of Glycyl-tRNA Synthetase in Complex with tRNA Suggest Multiple Conformational States in Glycylation

Qin

Hao

Tian

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The molecular basis for catalysis by human glycyl-tRNA synthetase (hGlyRS) is unclear. Results: hGlyRS-tRNA complex structures are reported, and the molecular details for enzymatic recognition are elucidated. Conclusion: hGlyRS catalysis involves multiple conformational changes, and insertions 1 and 3 may facilitate tRNA binding. Significance: Understanding the catalytic pathway also provides insights into the role of hGlyRS in disease.

show abstract

“…Onset of symptoms ranges from early childhood to early adulthood with distal muscle weakness and wasting occurring in the distal extremities, more evident in the legs compared to the arms. A sensory deficit may occur in the feet and lower extremities [57] . There is one family from south France found to have an axonal neuropathy with cardiac involvement and an autosomal dominant inheritance.…”

Section: Wwwnaturecom/aps Boudoulas Kd Et Almentioning

confidence: 99%

Beyond membrane channelopathies: alternative mechanisms underlying complex human disease

Boudoulas

Mohler

2011

Acta Pharmacol Sin

View full text Add to dashboard Cite

Phenotype of Charcot–Marie–Tooth disease Type 2

Cited by 54 publications

References 48 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

Cocrystal Structures of Glycyl-tRNA Synthetase in Complex with tRNA Suggest Multiple Conformational States in Glycylation

Beyond membrane channelopathies: alternative mechanisms underlying complex human disease

Contact Info

Product

Resources

About