TY - JOUR
T1 - Apparent genotype-phenotype correlation in childhood, adolescent, and adult Chediak-Higashi syndrome
AU - Karim, Mohammad A.
AU - Suzuki, Koji
AU - Fukai, Kazuyoshi
AU - Oh, Jangsuk
AU - Nagle, Deborah L.
AU - Moore, Karen J.
AU - Barbosa, Ernest
AU - Falik-Borenstein, Tzipora
AU - Filipovich, Alexandra
AU - Ishida, Yasushi
AU - Kivrikko, Sirpa
AU - Klein, Christoph
AU - Kreuz, Friedmar
AU - Levin, Alex
AU - Miyajima, Hiroaki
AU - Regueiro, Jose
AU - Russo, Carolyn
AU - Uyama, Eiichiro
AU - Vierimaa, Outi
AU - Spritz, Richard A.
PY - 2002/2/15
Y1 - 2002/2/15
N2 - 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.
AB - 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.
KW - Beige
KW - CHS1 gene
KW - Chediak-Higashi syndrome
KW - LYST
UR - http://www.scopus.com/inward/record.url?scp=18244405827&partnerID=8YFLogxK
U2 - 10.1002/ajmg.10184
DO - 10.1002/ajmg.10184
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C2 - 11857544
AN - SCOPUS:18244405827
SN - 0148-7299
VL - 108
SP - 16
EP - 22
JO - American Journal of Medical Genetics
JF - American Journal of Medical Genetics
IS - 1
ER -