Introduction: We identified a family with a new syndrome characterized by progressive motor dysfunction, peripheral neuropathy, deafness, blindness, retinitis pigmentosa, hyperintense changes in posterior limb of internal capsule, subcortical white matter and dentate nucleus of cerebellum. Here we present our research on a family harboring progressive neurodegenerative disease from eastern Turkey with recessive trait which is not named before.

Methods: Considering the fact that the trait is recessive, whole-exome sequencing and runs of homozygosity (ROH) analysis were conducted.

Results: A homozygous mutation (c.853_871del19) was found in the gene coding the kinesin light chain 4 protein (KLC4) in 3 affected children whereas unaffected parents and two siblings were heterozygous and one sibling was homozygous wild-type. The 19bp deletion in exon 6 was generating a stop codon and thus a truncated mRNA and protein. Although the function of KLC4 has not been investigated, Kinesin Light Chain family proteins make a protein complex with kinesin heavy chain (KHC) proteins and they perform cargo transport task trough microtubules in neurons. The c.853_871del19 mutation in exon 6 causing a stop codon formation at the 288th aa. Since the homozygous c.853_871del19 mutation segregated with disease in the family and the mutation was not present either in in-house 700 exome samples or in public databases we suggest that this particular mutation in KLC4 gene is disease causing. In addition, the nature of mutation leading a truncated protein that lacks the 342 C-terminal residues containing all tetratrico peptide repeat region (TPR) providing further evidence that the c.853_871del19 deletion impair KLC4 function.

Conclusions: We suggest that the reported mutation in KLC4 gene results in a progressive neurological disease which makes KLC4 gene a new member of disease-associated gene.

Patient Care: Investigation of this causative gene and finding new mutations that affect its function may lead to new gene therapies that may stop this progressive disease.

Learning Objectives: By the conclusion of this session, participants should be able to: 1)Describe the importance of mutations of KLC4 gene in neurodegeneration. 2)have an idea about new neurodegeneration syndrome presenting by progressive motor dysfunction, peripheral neuropathy, deafness, blindness, retinitis pigmentosa, hyperintense changes in posterior limb of internal capsule, subcortical white matter and dentate nucleus of cerebellum

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