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Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms

T Kondo1, K Takahashi, N Kohara

  • 1Department of Immunology, National Institute of Neuroscience, National Center for Neurology and Psychiatry, Kodairo, Tokyo, Japan.

Neurology
|October 9, 2002
PubMed

Insights

Nasu-Hakola disease (NHD) in Japanese patients is often caused by mutations in the DAP12 gene, leading to presenile dementia and bone cysts. Genetic analysis revealed loss-of-function mutations in five out of six cases studied.

Area of Science:

  • Genetics
  • Neurology
  • Bone Biology

Background:

  • Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder.
  • NHD presents with presenile dementia and bone cysts.
  • Previous studies identified DAP12 gene deletions in Finnish NHD patients.

Purpose of the Study:

  • To investigate the genetic basis of NHD in Japanese patients.
  • To identify mutations in the DAP12 gene in Japanese NHD cases.
  • To understand the genetic heterogeneity of NHD in Japan.

Main Methods:

  • Genetic analysis of DAP12 alleles in six Japanese NHD patients.
  • Mutation screening including deletion and point mutation analysis.
  • Assessment of DAP12 protein expression in a patient without mutation.

Main Results:

  • Five of the six Japanese NHD patients had loss-of-function mutations in DAP12.
  • Identified mutations included a single-base deletion and a novel point mutation.
  • One patient without DAP12 mutation showed normal protein expression, suggesting other genetic forms.

Conclusions:

  • The DAP12 gene is a significant cause of NHD in Japanese populations.
  • Japanese NHD exhibits genetic heterogeneity, with at least three forms related to DAP12.
  • Further research is needed to elucidate the genetic basis in all Japanese NHD cases.

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