Document Detail

Apparent genotype-phenotype correlation in childhood, adolescent, and adult Chediak-Higashi syndrome.
MedLine Citation:
PMID:  11857544     Owner:  NLM     Status:  MEDLINE    
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.
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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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of medical genetics     Volume:  108     ISSN:  0148-7299     ISO Abbreviation:  Am. J. Med. Genet.     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-02-21     Completed Date:  2002-08-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7708900     Medline TA:  Am J Med Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16-22     Citation Subset:  IM    
Copyright Information:
Copyright 2002 Wiley-Liss, Inc.
Human Medical Genetics Program, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
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MeSH Terms
Chediak-Higashi Syndrome / genetics*,  physiopathology
Child, Preschool
Chromosomes, Artificial, Bacterial
Chromosomes, Artificial, P1 Bacteriophage
Codon, Nonsense
Conserved Sequence
DNA Mutational Analysis
Evolution, Molecular
Frameshift Mutation
Fungal Proteins / genetics*
Linkage (Genetics)
Mutation, Missense
Sequence Analysis, DNA
Grant Support
Reg. No./Substance:
0/CSH1 protein, Candida albicans; 0/Codon, Nonsense; 0/Fungal Proteins

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