Monoallelic KIF1A-related disorders: a multicenter cross sectional study and systematic literature review

source extracted confidence: high 2026-04-09
#cross-sectional-studies #dna-copy-number-variations #heterozygote #humans #kinesins

Monoallelic KIF1A-related disorders: a multicenter cross sectional study and systematic literature review

Vecchia et al., 2022 | J Neurol | Systematic Review

Citation

Vecchia Stefania Della, Tessa Alessandra, ... Santorelli Filippo Maria. Monoallelic KIF1A-related disorders: a multicenter cross sectional study and systematic literature review. J Neurol. 2022-Jan;269(1):437-450. doi:10.1007/s00415-021-10792-3

Abstract

BACKGROUND: Monoallelic variants in the KIF1A gene are associated with a large set of clinical phenotypes including neurodevelopmental and neurodegenerative disorders, underpinned by a broad spectrum of central and peripheral nervous system involvement. METHODS: In a multicenter study conducted in patients presenting spastic gait or complex neurodevelopmental disorders, we analyzed the clinical, genetic and neuroradiological features of 28 index cases harboring heterozygous variants in KIF1A. We conducted a literature systematic review with the aim to comparing our findings with previously reported KIF1A-related phenotypes. RESULTS: Among 28 patients, we identified nine novel monoallelic variants, and one a copy number variation encompassing KIF1A. Mutations arose de novo in most patients and were prevalently located in the motor domain. Most patients presented features of a continuum ataxia-spasticity spectrum with only five cases showing a prevalently pure spastic phenotype and six presenting congenital ataxias. Seventeen mutations occurred in the motor domain of the Kinesin-1A protein, but location of mutation did not correlate with neurological and imaging presentations. When tested in 15 patients, muscle biopsy showed oxidative metabolism alterations (6 cases), impaired respiratory chain complexes II + III activity (3/6) and low CoQ10 levels (6/9). Ubiquinol supplementation (1gr/die) was used in 6 patients with subjective benefit. CONCLUSIONS: This study broadened our clinical, genetic, and neuroimaging knowledge of KIF1A-related disorders. Although highly heterogeneous, it seems that manifestations of ataxia-spasticity spectrum disorders seem to occur in most patients. Some patients also present secondary impairment of oxidative metabolism; in this subset, ubiquinol supplementation therapy might be appropriate.

Key Findings

Among 28 patients, we identified nine novel monoallelic variants, and one a copy number variation encompassing KIF1A. Mutations arose de novo in most patients and were prevalently located in the motor domain. Most patients presented features of a continuum ataxia-spasticity spectrum with only five cases showing a prevalently pure spastic phenotype and six presenting congenital ataxias. Seventeen mutations occurred in the motor domain of the Kinesin-1A protein, but location of mutation did not co

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population subjective benefit
Sample Size 28
Age Range See abstract
Condition See abstract

MeSH Terms

  • Cross-Sectional Studies
  • DNA Copy Number Variations
  • Heterozygote
  • Humans
  • Kinesins
  • Mutation
  • Phenotype
  • Spastic Paraplegia, Hereditary

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Multicenter Study, Systematic Review
  • Vertical: coq10

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09