Publication
Title
Targeted high-throughput sequencing identifies mutations in **atlastin-1** as a cause of hereditary sensory neuropathy type I
Author
Abstract
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.
Language
English
Source (journal)
The American journal of human genetics. - New York, N.Y.
Publication
New York, N.Y. : 2011
ISSN
0002-9297
Volume/pages
88:1(2011), p. 99-105
ISI
000286501500010
Full text (Publishers DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
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Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 17.05.2011
Last edited 10.04.2017
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