title: Two novel CHS1 (LYST) mutations: clinical correlations in an infant with Chediak-Higashi syndrome.
abstract: Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disease characterized by variable degrees of oculocutaneous albinism, recurrent infections, and a mild bleeding tendency, with late neurologic dysfunction. Most patients also undergo an accelerated phase of lymphohistiocytosis and die at an early age unless they receive an allogeneic hematopoietic stem cell transplant (SCT). Mutations in the CHS1 (LYST) gene result in CHS. Here, we describe an adopted infant who is compound heterozygous for two novel CHS1 gene mutations, both of which are predicted to result in truncated proteins. The two mutations are a nonsense mutation (c.1540 C>T, CGA>TGA, R514X) in exon 5 and a one base pair deletion (del c.9893T, F3298fsX3304) in exon 43, coding for part of the CHS1 protein's BEACH domain. These two newly described mutations are expected to give rise to a severe phenotype and, indeed, the patient had absolutely no cytotoxicity by natural killer cells or cytotoxic lymphocytes prior to his allogeneic SCT.
authors.affiliation: Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Wafika
authors.initials: W
authors.lastname: Zarzour
authors.forename: Robert
authors.initials: R
authors.lastname: Kleta
authors.forename: Haydar
authors.initials: H
authors.lastname: Frangoul
authors.forename: Pim
authors.initials: P
authors.lastname: Suwannarat
authors.forename: Anna
authors.initials: A
authors.lastname: Jeong
authors.forename: Su Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Alan S
authors.initials: AS
authors.lastname: Wayne
authors.forename: Meral
authors.initials: M
authors.lastname: Gunay-Aygun
authors.forename: James
authors.initials: J
authors.lastname: White
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D001792:Blood Platelets / Q000648:ultrastructure; D002609:Chediak-Higashi Syndrome / Q000235:genetics* / Q000473:pathology; D018389:Codon, Nonsense; D005091:Exons; D006197:Hair / Q000648:ultrastructure; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D046529:Microscopy, Electron, Transmission; D009504:Neutrophils / Q000648:ultrastructure; D011506:Proteins / Q000235:genetics*; D033921:Vesicular Transport Proteins
chemical_list: D018389:Codon, Nonsense; C102161:LYST protein, human; D011506:Proteins; D033921:Vesicular Transport Proteins