arg-cys substitution at codon 1246 of the human myosin Va gene is not associated with Griscelli syndrome

J Invest Dermatol. 2000 Apr;114(4):731-3. doi: 10.1046/j.1523-1747.2000.00933.x.


Myosin Va is an actin-associated motor protein involved in organelle transport such as melanosomes and neuron synaptic vesicles and has always been proposed as the candidate gene for the autosomal recessive Griscelli-Pruniéras syndrome, one of the silvery hair syndromes, which is a lethal disease combining immunodeficiency and neurologic and pigmentary abnormalities. Thus far, two mutations in the myosin Va gene have been described to be associated with this syndrome. One of these mutations was a homozygous mis-sense mutation causing an arginine to cysteine alteration at codon 1246. Because we also found this particular substitution after mutation analysis of a Griscelli patient, we checked its relevance in a control group of 124 unrelated healthy individuals and found it to be present, even in homozygous state, in normal unaffected individuals. It is clear that this arg1246cys substitution is a polymorphism occurring in the human population and not occurring in association with Griscelli syndrome. Distinguishing a polymorphism from a bona fide mutation is of utmost importance and has major ethical implications with regard to prenatal genetic counseling in affected families.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albinism / genetics
  • Amino Acid Substitution / genetics
  • Humans
  • Immunologic Deficiency Syndromes / genetics*
  • Mutation, Missense
  • Myosins / genetics*
  • Phenotype
  • Point Mutation
  • Reverse Transcriptase Polymerase Chain Reaction


  • Myosins