Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Enzyme
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Query: UMLS:C0851184 (
thinning
)
11,252
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
KIF1A
is a brain-specific anterograde motor protein that transports cargoes towards the plus-ends of microtubules. Many variants of the
KIF1A
gene have been associated with neurodegenerative diseases and developmental delay. Homozygous mutations of
KIF1A
have been identified in a recessive subtype of hereditary spastic paraplegia (HSP), SPG30. In addition,
KIF1A
mutations have been found in pure HSP with autosomal dominant inheritance. Here we report the first case of familial complicated HSP with a
KIF1A
mutation transmitted in autosomal dominant inheritance. A heterozygous p.T258M mutation in
KIF1A
was found in a Korean family through targeted exome sequencing. They displayed phenotypes of mild intellectual disability with language delay, epilepsy, optic nerve atrophy,
thinning
of corpus callosum, periventricular white matter lesion, and microcephaly. A structural modeling revealed that the p.T258M mutation disrupted the binding of
KIF1A
motor domain to microtubules and its movement along microtubules. Assays of peripheral accumulation and proximal distribution of
KIF1A
motor indicated that the
KIF1A
motor domain with p.T258M mutation has reduced motor activity and exerts a dominant negative effect on wild-type
KIF1A
. These results suggest that the p.T258M mutation suppresses
KIF1A
motor activity and induces complicated HSP accompanying intellectual disability transmitted in autosomal dominant inheritance.
...
PMID:Autosomal dominant transmission of complicated hereditary spastic paraplegia due to a dominant negative mutation of KIF1A, SPG30 gene. 2897 May 74
