BACKGROUND: Autosomal-recessive hereditary spastic paraplegias (AR-HSP) consist 
of a genetically diverse group of neurodegenerative diseases characterised by 
pyramidal tracts dysfunction. The causative genes for many types of AR-HSP 
remain elusive. We tried to identify the gene mutation for AR-HSP with 
cerebellar ataxia and neuropathy.
METHODS: This study included two patients in a Japanese family with their 
parents who are first cousins. Neurological examination and gene analysis were 
conducted in the two patients and two normal family members. We undertook 
genome-wide linkage analysis employing single nucleotide polymorphism arrays 
using the two patients' DNAs and exome sequencing using one patient's sample.
RESULTS: We detected a homozygous missense mutation (c.4189T>G, p.F1397V) in the 
lysosomal trafficking regulator (LYST) gene, which is described as the causative 
gene for Chédiak-Higashi syndrome (CHS). CHS is a rare autosomal-recessive 
syndrome characterised by hypopigmentation, severe immune deficiency, a bleeding 
tendency and progressive neurological dysfunction. This mutation was 
co-segregated with the disease in the family and was located at well-conserved 
amino acid. This LYST mutation was not found in 200 Japanese control DNAs. 
Microscopic observation of peripheral blood in the two patients disclosed large 
peroxidase-positive granules in both patients' granulocytes, although they had 
no symptoms of immune deficiency or bleeding tendency.
CONCLUSIONS: We diagnosed these patients as having adult CHS presenting spastic 
paraplegia with cerebellar ataxia and neuropathy. The clinical spectrum of CHS 
is broader than previously recognised. Adult CHS must be considered in the 
differential diagnosis of AR-HSP.