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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Guelly, C; Zhu, PP; Leonardis, L; Papic, L; Zidar, J; Schabhüttl, M; Strohmaier, H; Weis, J; Strom, TM; Baets, J; Willems, J; De Jonghe, P; Reilly, MM; Fröhlich, E; Hatz, M; Trajanoski, S; Pieber, TR; Janecke, AR; Blackstone, C; Auer-Grumbach, M.
Targeted high-throughput sequencing identifies mutations in atlastin-1 as a cause of hereditary sensory neuropathy type I.
Am J Hum Genet. 2011; 88(1):99-105 Doi: 10.1016/j.ajhg.2010.12.003 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Auer-Grumbach Michaela
Gülly Christian
Co-Autor*innen der Med Uni Graz
Fröhlich Eleonore
Hofstadler Martina
Papic Lea
Pieber Thomas
Strohmaier Heimo
Trajanoski Slave

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Hereditary sensory neuropathy type I (HSN I) is an axonal form of autosomal-dominant hereditary motor and sensory neuropathy distinguished by prominent sensory loss that leads to painless injuries. Unrecognized, these can result in delayed wound healing and osteomyelitis, necessitating distal amputations. To elucidate the genetic basis of an HSN I subtype in a family in which mutations in the few known HSN I genes had been excluded, we employed massive parallel exon sequencing of the 14.3 Mb disease interval on chromosome 14q. We detected a missense mutation (c.1065C>A, p.Asn355Lys) in atlastin-1 (ATL1), a gene that is known to be mutated in early-onset hereditary spastic paraplegia SPG3A and that encodes the large dynamin-related GTPase atlastin-1. The mutant protein exhibited reduced GTPase activity and prominently disrupted ER network morphology when expressed in COS7 cells, strongly supporting pathogenicity. An expanded screen in 115 additional HSN I patients identified two further dominant ATL1 mutations (c.196G>C [p.Glu66Gln] and c.976 delG [p.Val326TrpfsX8]). This study highlights an unexpected major role for atlastin-1 in the function of sensory neurons and identifies HSN I and SPG3A as allelic disorders.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Base Sequence -
COS Cells -
Cercopithecus aethiops -
Chromosomes, Human, Pair 14 - genetics
Endoplasmic Reticulum - enzymology
Exons -
Female -
GTP Phosphohydrolases - genetics
GTP-Binding Proteins -
Genes, Dominant -
Hereditary Sensory and Autonomic Neuropathies - genetics
High-Throughput Nucleotide Sequencing -
Humans -
Male -
Membrane Proteins -
Molecular Sequence Data -
Mutation -
Mutation, Missense -
Sequence Analysis, DNA -
Spastic Paraplegia, Hereditary - genetics

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