Variants in KIF1A gene in dominant and sporadic forms of hereditary spastic paraparesis.

Abstract:

:KIF1A gene encodes the kinesin 1a protein, an axonal motor protein working in cargo transport along neurites. Variants in KIF1A were identified in different forms of neurodegenerative diseases with dominant and recessive inheritance. Homozygous recessive mutations were found in the hereditary sensory and autonomic neuropathy type 2, HSAN2 and in a recessive subtype of hereditary spastic paraparesis, SPG30. De novo heterozygous dominant variants were found both in a dominant form of SPG30 (AD-SPG30) with one single family reported and in patients with different forms of progressive neurodegenerative diseases. We report the results of a genetic screening of 192 HSP patients, with the identification of four heterozygous variants in KIF1A in four cases, two of whom with family history for the disease. Three of the four variants fall within the motor domain, a frequent target for variants related to the AD-SPG30 subtype. The fourth variant falls downstream the motor domain in a region lacking any functional domain. The KIF1A-related patients show clinical pictures overlapping the known AD-SPG30 phenotype including pure and complicated forms with few differences. Of note, one of the families, originating from the Sicily island, carries the same variant p.S69L detected in the first AD-SPG30 family of Finnish origin reported; differently from the first one, the latter family shows a wide intra-familial phenotype variability. Overall, these data reveal a very low frequency of the AD-SPG30 subtype while confirming the presence of amino acid residues in the motor domain representing preferential targets for mutations, thereby supporting their functional relevance in kinesin 1a activity.

journal_name

J Neurol

journal_title

Journal of neurology

authors

Citterio A,Arnoldi A,Panzeri E,Merlini L,D'Angelo MG,Musumeci O,Toscano A,Bondi A,Martinuzzi A,Bresolin N,Bassi MT

doi

10.1007/s00415-015-7899-9

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

2684-90

issue

12

eissn

0340-5354

issn

1432-1459

pii

10.1007/s00415-015-7899-9

journal_volume

262

pub_type

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