Rinsho Shinkeigaku (Clinical Neurology)

The 48th Annual Meeting of the Japanese Society of Neurology

Molecular genetic analysis of amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) in the Kii peninsula

Kenju Hara1), Ryozo Kuwano2), Akinori Miyashita2), Yasumasa Kokubo3), Ryogen Sasaki3), Yasuo Nakahara4), Jun Goto4), Masatoyo Nishizawa1), Shigeki Kuzuhara3) and Shoji Tsuji4)

1)Department of Neurology, Brain Research Institute, Niigata University
2)Genome Science Branch, Center for Bioresource-Based Research, Niigata University Brain Research Institute
3)Department of Neurology, Mie University, Graduate School of Medicine
4)Department of Neurology, University of Tokyo, Graduate School of Medicine

Recent clinical research have revealed that more than 70% of the patients with ALS/PDC, which is highly prevalent in Hohara area in the Kii peninsula, have family history. 80% of Guamanian patients, who have identical pathological findings to those of ALS/PDC in Kii, are also known to have family history with non-Mendelian trait. These facts suggest strong genetic predisposition to ALS/PDC in both Kii and Guam. However, no genes associated with ALS/PDC have been identified by molecular genetic studies using candidate gene approach. To identify the causative or susceptibility genes for ALS/PDC, we have conducted a genomewide linkage analysis for five families with ALS/PDC in Hohara. The fact that affected individuals were ascertained in successive generations suggest an autosomal dominant (AD) inheritance, while the presence of consanguinity suggests an autosomal recessive (AR) inheritance. Although we can raise possibilities of AD model with incomplete penetrance or AR model with high gene frequency (pseudo-dominant model), the mode of inheritance of ALS/PDC families is complicated and controversial. Therefore, we are also conducting model-free (non-parametric) linkage analysis to identify the disease locus without setting mode of inheritance. More family members and detailed clinical evaluations are required to obtain the convincing evidence of linkage.

(CLINICA NEUROL, 47: 974－976, 2007)
key words: Kii ALS/PDC, genomewide linkage analysis

(Received: 16-May-07)