Mar 26, 2013

Atypical Chédiak-Higashi syndrome with attenuated phenotype: three adult siblings homozygous for a novel LYST deletion and with neurodegenerative disease

Orphanet Journal of Rare Diseases
James D Weisfeld-AdamsCatherine Cho

Abstract

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. 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. 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. We further characterize the neurologic features of the attenuated form of CHS, and discuss pathophysiologic mechanisms underlying the neurodegenerative components ...Continue Reading

  • References23
  • Citations11

References

  • References23
  • Citations11

Citations

Mentioned in this Paper

Asparagine
Immunologic Deficiency Syndromes
Immune System Diseases
Sister
Genetic Screening Method
Degenerative Diseases, Spinal Cord
Nerve Degeneration
LYST wt Allele
Gene Deletion Abnormality
Nucleic Acid Sequencing

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