Abstract Details

Title Pathology of Frontotemporal Dementia with LGMD Caused by DNAJB6 Mutation

Topic Behavioral Neurology

Presentation(s) P07 - (-)

Poster/Presentation
Number 160

Objective

Background BACKGROUND: LGMD type 1D is caused by mutations in DNAJB6, a chaperon protein similar to valosin-containing protein (VCP). The VCP gene mutations cause a rare autosomal dominant disorder named inclusion body myopathy with Paget's disease of bone and FTD (IBMPFD). The muscle pathology of LGMD1D shares common features with that of IBMPFD. In addition, DNAJB6 may also play a role in polyglutamine aggregation and Lewy body production in specific neurons.

Design/Methods DESIGN/METHODS: A 61 year old male complained of lower extremity weakness. His father and 3 siblings showed similar symptoms. The patient was diagnosed as LGMD in 1992. Symptoms at proximal muscles gradually deteriorated. In 2005, he became stubborn and angry toward his family. These symptoms gradually deteriorated. In August 2007, chest CT indicated a tumor in the right lung, and pneumonia developed often. In October 2007, the patient died of septic shock and renal failure. Autopsy and DNA sequencing were performed.

Results RESULTS: Missense mutation of DNAJB6 c.279C>G (p. Phe93Leu) was identified. In pathological findings, primary squamous cell carcinoma and small cell carcinoma were observed in the right lung with adrenal metastasis of small cell carcinoma. Death was from respiratory insufficiency due to pneumonia and sepsis. Mild atrophy was present in the front and temporal lobes. Tau protein, pTDP-43, FUS and Lewy body immunoreactivity was not observed, but ubiquitin-positive aggregates were observed. There was a severe reduction of DNAJB6 in the cerebral cortex. Muscle pathology showed dystrophic changes with vacuoles with TDP-43 and DNAJB6 accumulation.

Conclusions CONCLUSIONS: Autopsy findings revealed FTD with LGMD1D due to a DNAJB6 mutation. This case may represent a new disease due to the pathological mechanism similar to VCP mutation.

Authors/Disclosures
Ichiro Yabe, MD, PhD (Hokkaido University) PRESENTER	Dr. Yabe has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Dr. Yabe has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for DaiichiSankyo. Dr. Yabe has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for SumitomoPharma. Dr. Yabe has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for KyowaKirin. Dr. Yabe has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alnylam Japan. Dr. Yabe has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eli Lilly Japan. The institution of Dr. Yabe has received research support from Toppan. The institution of Dr. Yabe has received research support from Ceres. The institution of Dr. Yabe has received research support from Hakuyo-Kai. The institution of Dr. Yabe has received research support from Choan-Kai.
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Pietro Annovazzi	No disclosure on file

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