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

Autori
Rohkamm, B. ; Reilly, M.M. ; Lochmüller, Hanns ; Schlotter-Weigel, B. ; Barišić, Nina ; Schöls, L. ; Nicholson, G. ; Pareyson, D. ; Laurà , M. ; Janecke, A.R. ; Miltenberger-Miltenyi, G. ; John, E. ; Fischer, C. ; Grill, F. ; Wakeling, W. ; Davis, M. ; Pieber, T.R. ; Auer-Grumbach, Michaela

Izvornik
Journal of the Neurological Sciences (0022-510X) 263 (2007), 1-2; 100-106

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
HMN V; CMT 2; genetics; Charcot-marie-tooth disease type 2d. Cmt2; Distal hereditary motor neuropathy; Dhmn; Bscl2; Gars; Hspb1; Hspb8

Sažetak
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. Exon 3 of the BSCL2 gene was screened in further 69 individuals with an unclassified dHMN phenotype or diagnosed as hereditary spastic paraplegia (HSP) complicated by pure motor neuropathy. RESULTS: Four patients diagnosed with dHMN-V or 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.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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