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Correspondence |

Haplotype-Phenotype Correlations in Kindreds With the N279K Mutation in the Tau Gene

Bryan K. Woodruff, MD; Yasuhiko Baba, MD; Michael L. Hutton, PhD; Zbigniew K. Wszolek, MD; Yoshio Tsuboi, MD; Tomonori Kobayashi, MD; Bernardino Ghetti, MD; Kunimasa Arima, MD; Minoru Yasuda, MD; Olivier Rascol, MD
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Copyright 2004 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

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Arch Neurol. 2004;61(8):1327-1327. doi:10.1001/archneur.61.8.1327-a
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The recent article by Soliveri et al1 identifies an Italian kindred with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) with the N279K mutation. The clinical phenotype is similar to that described in other kindreds with the N279K mutation, with prominent parkinsonism and personality changes early in the course of the disease.2

The observation that personality changes preceded parkinsonism in the patient described by Soliveri and colleagues is of interest because isolated personality changes at symptom onset occur in only a few previously described patients with the N279K mutation. We have systematically reviewed the records of several kindreds with this mutation.

Tau haplotyping was performed in 28 DNA samples from 5 N279K families. Tau haplotypes (H1/H1, H1/H2, and H2/H2) were assessed using polymerase chain reaction amplification with a deletion-insertion polymorphism in intron 9. Clinical and genetic data are shown in the Table.

Table Grahic Jump LocationTable. Clinical and Genetic Data in Patients With the N279K Tau Mutation

The earlier age at symptom onset and longer disease duration are notable in patients with the H1/H2 genotype, although the small sample size limits these observations. It is also interesting that 1 patient with the H1/H2 genotype initially developed isolated personality changes, a finding in only 3 patients in our series. These early neuropsychiatric changes parallel findings of neuropsychological dysfunction in carriers of the N279K mutation prior to the onset of motor symptoms.3 Presence of the H2 allele may predispose patients to these features, but analysis of other kindreds is needed given the small number of described cases. Determining the tau haplotype of individuals in the Italian kindred will be of particular interest in this regard. Further collaborative studies are required to determine if the tau haplotype affects not only risk for disease development but also clinical phenotype.

AUTHOR INFORMATION

Correspondence: Dr Wszolek, 4500 San Pablo Rd, Jacksonville, FL 32224 (wszolek.zbigniew@mayo.edu).

REFERENCES

Soliveri  P, Rossi  G, Monza  D.  et al.  A case of dementia parkinsonism resembling progressive supranuclear palsy due to mutation in the tau protein gene. Arch Neurol 2003;601454- 1456
PubMed
Ghetti  B, Hutton  M, Wszolek  Z. Frontotemporal dementia and parkinsonism linked to chromosome 17 associated with tau gene mutations (FTDP-17T). In: , ed. Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders. Basel, Switzerland: ISN Neuropath Press; 2003;:86-- 102
Ferman  TJ, McRae  CA, Arvanitakis  Z.  et al.  Early and pre-symptomatic neuropsychological dysfunction in the PPND family with the N279K tau mutation. Parkinsonism Relat Disord 2003;9265- 270
PubMed

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Table Grahic Jump LocationTable. Clinical and Genetic Data in Patients With the N279K Tau Mutation

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Soliveri  P, Rossi  G, Monza  D.  et al.  A case of dementia parkinsonism resembling progressive supranuclear palsy due to mutation in the tau protein gene. Arch Neurol 2003;601454- 1456
PubMed
Ghetti  B, Hutton  M, Wszolek  Z. Frontotemporal dementia and parkinsonism linked to chromosome 17 associated with tau gene mutations (FTDP-17T). In: , ed. Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders. Basel, Switzerland: ISN Neuropath Press; 2003;:86-- 102
Ferman  TJ, McRae  CA, Arvanitakis  Z.  et al.  Early and pre-symptomatic neuropsychological dysfunction in the PPND family with the N279K tau mutation. Parkinsonism Relat Disord 2003;9265- 270
PubMed

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