Genotypes

More than 300 mutant alleles have been identified in Gaucher disease. Mistry PK, Weinthal JA, Weinreb NJ. Disease state awareness in Gaucher disease: a Q&A expert roundtable discussion. Clin Adv Hematol Oncol. 2012;10:1-16.  Clinical expression of Gaucher disease generally cannot be accurately predicted solely by mutation analysis. For the majority of mutations the genotype/phenotype relationship is weak but there are some close genotype/phenotype relationships including:

  • N37OS and 84GG mutations are primarily responsible for the relatively high incidence in Ashkenazi Jews (up to approximately 1 in 850).   Mistry PK, Cappellini M, Lukina E, et al. Consensus Conference: a reappraisal of Gaucher disease – diagnosis and disease management algorithms. Am J Hematol 2011;86(1):110-115

    Grabowski GA, Petsko GA, Kolodny EH. Chapter 146: Gaucher disease. Valle D, Beaudet AL, Vogelstein B, et al, eds. The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw Hill; 2013. Accessed July 6, 2015.
  • N370S mutation is associated with type 1 disease and precludes neuronopathic involvement. Grabowski GA, Petsko GA, Kolodny EH. Chapter 146: Gaucher disease. Valle D, Beaudet AL, Vogelstein B, et al, eds. The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw Hill; 2013. Accessed July 6, 2015.
  • L444P mutation found in the Swedish Norrbottnian population generally predicts neuronopathic type 3 disease. Grabowski GA, Petsko GA, Kolodny EH. Chapter 146: Gaucher disease. Valle D, Beaudet AL, Vogelstein B, et al, eds. The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw Hill; 2013. Accessed July 6, 2015.
  • The D409H mutation is strongly associated with type 3c disease affecting cardiac function. Grabowski GA, Petsko GA, Kolodny EH. Chapter 146: Gaucher disease. Valle D, Beaudet AL, Vogelstein B, et al, eds. The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw Hill; 2013. Accessed July 6, 2015.