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Gaucher disease: In vivo evidence for allele dose leading to neuronopathic and nonneuronopathic phenotypes
Author(s) -
Zhao Huiquan,
Bailey Laurie A.,
Elsas Louis J.,
Grinzaid Karen A.,
Grabowski Gregory A.
Publication year - 2002
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.10029
Subject(s) - allele , phenotype , genetics , disease , biology , in vivo , medicine , gene
Gaucher disease, a common lysosomal storage disorder, is associated with mutations at the acid β‐glucosidase (GCase) locus. Two affected individuals are described to share a common mutant allele, but manifest different clinical categorical phenotypes. A 57‐year‐old female, with Gaucher disease type 1 and Cherokee ancestry, was homozygous for a rare mutant allele encoding Lys79Asn (K79N). A 2‐year‐old Caucasian male, with Gaucher disease type 3 and Cherokee ancestry, was a heteroallelic homozygote for this same allele (K79N) and a novel complex mutation (null allele). The shared alleles were identical as determined by complete gene sequencing, suggesting a founder effect. The discrepant phenotypes (types 1 and 3) in these two patients provide support for a threshold of residual activity necessary to “protect” the central nervous system (CNS) from the pathogenic effects of Gaucher disease, indicating an allele dose‐effect. Designation of genotype associations with specific phenotypes must be assessed with this perspective. © 2003 Wiley‐Liss, Inc.