Apparent genotype-phenotype correlation in childhood, adolescent, and adult Chediak-Higashi syndrome

Mohammad A. Karim, Koji Suzuki, Kazuyoshi Fukai, Jangsuk Oh, Deborah L. Nagle, Karen J. Moore, Ernest Barbosa, Tzipora Falik-Borenstein, Alexandra Filipovich, Yasushi Ishida, Sirpa Kivrikko, Christoph Klein, Friedmar Kreuz, Alex Levin, Hiroaki Miyajima, Jose Regueiro, Carolyn Russo, Eiichiro Uyama, Outi Vierimaa, Richard A. Spritz

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147 Scopus citations


Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by severe immunologic defects, reduced pigmentation, bleeding tendency, and progressive neurological dysfunction. Most patients present in early childhood and die unless treated by bone marrow transplantation. About 10-15% of patients exhibit a much milder clinical phenotype and survive to adulthood, but develop progressive and often fatal neurological dysfunction. Very rare patients exhibit an intermediate adolescent CHS phenotype, presenting with severe infections in early childhood, but a milder course by adolescence, with no accelerated phase. Here, we describe the organization and genomic DNA sequence of the CHS1 gene and mutation analysis of 21 unrelated patients with the childhood, adolescent, and adult forms of CHS. In patients with severe childhood CHS, we found only functionally null mutant CHS1 alleles, whereas in patients with the adolescent and adult forms of CHS we also found missense mutant alleles that likely encode CHS1 polypeptides with partial function. Together, these results suggest an allelic genotype-phenotype relationship among the various clinical forms of CHS.

Original languageEnglish
Pages (from-to)16-22
Number of pages7
JournalAmerican Journal of Medical Genetics
Issue number1
StatePublished - 15 Feb 2002
Externally publishedYes


FundersFunder number
National Institute of Arthritis and Musculoskeletal and Skin DiseasesR01AR039892


    • Beige
    • CHS1 gene
    • Chediak-Higashi syndrome
    • LYST


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