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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Windpassinger, C; Auer-Grumbach, M; Irobi, J; Patel, H; Petek, E; Hörl, G; Malli, R; Reed, JA; Dierick, I; Verpoorten, N; Warner, TT; Proukakis, C; Van den Bergh, P; Verellen, C; Van Maldergem, L; Merlini, L; De Jonghe, P; Timmerman, V; Crosby, AH; Wagner, K.
Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome.
Nat Genet. 2004; 36(3):271-276
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Autor/innen der Med Uni Graz:
Auer-Grumbach Michaela
Hörl Gerd
Malli Roland
Petek Erwin
Wagner Klaus
Windpassinger Christian
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Abstract:
Distal hereditary motor neuropathy (dHMN) or distal spinal muscular atrophy (OMIM #182960) is a heterogeneous group of disorders characterized by an almost exclusive degeneration of motor nerve fibers, predominantly in the distal part of the limbs. Silver syndrome (OMIM #270685) is a rare form of hereditary spastic paraparesis mapped to chromosome 11q12-q14 (SPG17) in which spasticity of the legs is accompanied by amyotrophy of the hands and occasionally also the lower limbs. Silver syndrome and most forms of dHMN are autosomal dominantly inherited with incomplete penetrance and a broad variability in clinical expression. A genome-wide scan in an Austrian family with dHMN-V (ref. 4) showed linkage to the locus SPG17, which was confirmed in 16 additional families with a phenotype characteristic of dHMN or Silver syndrome. After refining the critical region to 1 Mb, we sequenced the gene Berardinelli-Seip congenital lipodystrophy (BSCL2) and identified two heterozygous missense mutations resulting in the amino acid substitutions N88S and S90L. Null mutations in BSCL2, which encodes the protein seipin, were previously shown to be associated with autosomal recessive Berardinelli-Seip congenital lipodystrophy (OMIM #269700). We show that seipin is an integral membrane protein of the endoplasmic reticulum (ER). The amino acid substitutions N88S and S90L affect glycosylation of seipin and result in aggregate formation leading to neurodegeneration.
Find related publications in this database (using NLM MeSH Indexing)
Bone and Bones - abnormalities
GTP-Binding Protein gamma Subunits - genetics
Genetic Heterogeneity - genetics
Hereditary Motor and Sensory Neuropathies - genetics
Humans - genetics
Motor Neurons - pathology
Mutation, Missense - pathology
Paraparesis - genetics
Syndrome - genetics

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