BACKGROUND: Mutations in LYST, a gene encoding a putative lysosomal trafficking 
protein, cause Chédiak-Higashi syndrome (CHS), an autosomal recessive disorder 
typically characterized by infantile-onset hemophagocytic syndrome and 
immunodeficiency, and oculocutaneous albinism. A small number of reports of 
rare, attenuated forms of CHS exist, with affected individuals exhibiting 
progressive neurodegenerative disease beginning in early adulthood with 
cognitive decline, parkinsonism, features of spinocerebellar degeneration, and 
peripheral neuropathy, as well as subtle pigmentary abnormalities and 
subclinical or absent immune dysfunction.
METHODS: In a consanguineous Pakistani kindred with clinical phenotypes 
consistent with attenuated CHS, we performed SNP array-based homozygosity 
mapping and whole gene sequencing of LYST.
RESULTS: We identified three individuals homozygous for a novel six base pair 
in-frame deletion in LYST (c.9827_9832ATACAA), predicting the loss of asparagine 
and threonine residues from the LYST transcript (p.Asn3276_Thr3277del), and 
segregating with the phenotype in this family.
CONCLUSIONS: We further characterize the neurologic features of the attenuated 
form of CHS, and discuss pathophysiologic mechanisms underlying the 
neurodegenerative components of CHS. Attenuated CHS is phenotypically 
heterogenous and should be considered when young adults develop 
neurodegenerative disease and have pigmentary abnormalities. We briefly discuss 
surveillance and management of patients with CHS-related neurodegeneration.