Abstract:
BACKGROUND:The SCN8A gene on chromosome 12q13 encodes the voltage gated sodium channel Na(v)1.6, which is widely expressed in neurons of the CNS and PNS. Mutations in the mouse ortholog of SCN8A result in ataxia and other movement disorders. METHODS:We screened the 26 coding exons of SCN8A in 151 patients with inherited or sporadic ataxia. RESULTS:A 2 bp deletion in exon 24 was identified in a 9 year old boy with mental retardation, pancerebellar atrophy, and ataxia. This mutation, Pro1719ArgfsX6, introduces a translation termination codon into the pore loop of domain 4, resulting in removal of the C-terminal cytoplasmic domain and predicted loss of channel function. Three additional heterozygotes in the family exhibit milder cognitive and behavioural deficits including attention deficit hyperactivity disorder (ADHD). No additional occurrences of this mutation were observed in 625 unrelated DNA samples (1250 chromosomes). CONCLUSIONS:The phenotypes of the heterozygous individuals suggest that mutations in SCN8A may result in motor and cognitive deficits of variable expressivity, but the study was limited by lack of segregation in the small pedigree and incomplete information about family members. Identification of additional families will be required to confirm the contribution of the SCN8A mutation to the clinical features in ataxia, cognition and behaviour disorders.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Trudeau MM,Dalton JC,Day JW,Ranum LP,Meisler MHdoi
10.1136/jmg.2005.035667keywords:
subject
Has Abstractpub_date
2006-06-01 00:00:00pages
527-30issue
6eissn
0022-2593issn
1468-6244pii
jmg.2005.035667journal_volume
43pub_type
信件abstract::We report on a proband with both a Robertsonian translocation and Turner's syndrome. Study of the parental origin of the X chromosome performed by microsatellite analysis indicates paternal origin of the X chromosome (Xpat). The occurrence of chromosome aberrations as a consequence of interchromosomal interactions is ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
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abstract:BACKGROUND:Congenital chromosome abnormalities are relatively common in our species and among structural abnormalities the most common class is balanced reciprocal translocations. Determining the parental origin of de novo balanced translocations may provide insights into how and when they arise. While there is a gener...
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journal_title:Journal of medical genetics
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journal_title:Journal of medical genetics
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journal_title:Journal of medical genetics
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journal_title:Journal of medical genetics
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更新日期:1998-08-01 00:00:00
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journal_title:Journal of medical genetics
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journal_title:Journal of medical genetics
pub_type: 杂志文章
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更新日期:1997-09-01 00:00:00
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journal_title:Journal of medical genetics
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更新日期:2017-12-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
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更新日期:2017-09-18 00:00:00
abstract:BACKGROUND:Lysosomal protein profiling is being developed as a high throughput method to screen populations for lysosomal storage disorders (LSD). DESIGN:1415 blood spots from patients referred to a metabolic clinic for LSD were screened using a single multiplex assay for 14 proteins in a dried blood spot. RESULTS:Al...
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abstract::Evidence for linkage has been sought, in four pedigrees with Crouzon syndrome, between polymorphic markers known to be linked to the Saethre-Chotzen locus on 7p and another form of autosomal dominant craniosynostosis on 5q. The data we present exclude Crouzon syndrome as an allelic variant at either of these known cra...
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更新日期:1994-03-01 00:00:00