A familial FTD associated with C9orf72 repeat expansion and dysplastic gangliocytoma

Anders Paetau,Liisa Myllykangas,Mia Kero,Pentti J Tienari,John Hardy,Parastoo Momeni,Kin Mok,Raffaele Ferrari,Auli Verkkoniemi-Ahola,Olli Tynninen

doi:10.1186/1750-1326-8-s1-p60

Abstract

Background A hexanucleotide repeat expansion, in the chromosome 9 open reading frame 72 gene (C9orf72), has been identified the most common genetic cause of FTD/ALS. Here we describe the clinical, pathologic and genetic features of a Finnish C9orf72 expansion carrier, who developed a dysplastic gangliocytoma, a rare hamartoma of cerebellar granule cells, associated with PTEN mutations. In addition to the dysplastic gangliocytoma, the patient showed TDP43-pathology in the cortex and in the substantia nigra, and p62-positive/TDP43-negative inclusions in the cerebellar granule cells. His sister carried the same gene defect and showed similar type of TDP43/p62-pathology in her brain. Our findings confirm the clinical and pathological picture of C9orf72 mutation carriers is more heterogeneous than originally thought and warrant further studies on the possible involvement of PTEN pathway in the specific cerebellar granule cell pathology associated with C9orf72 expansion.

Highlights

A hexanucleotide repeat expansion, in the chromosome 9 open reading frame 72 gene (C9orf72), has been identified the most common genetic cause of FTD/ALS
A familial FTD associated with chromosome 9 open reading frame gene (C9orf72) repeat expansion and dysplastic gangliocytoma
Our findings confirm the clinical and pathological picture of C9orf72 mutation carriers is more heterogeneous than originally thought and warrant further studies on the possible involvement of PTEN pathway in the specific cerebellar granule cell pathology associated with C9orf72 expansion

Summary

Introduction

A hexanucleotide repeat expansion, in the chromosome 9 open reading frame 72 gene (C9orf72), has been identified the most common genetic cause of FTD/ALS. We describe the clinical, pathologic and genetic features of a Finnish C9orf expansion carrier, who developed a dysplastic gangliocytoma, a rare hamartoma of cerebellar granule cells, associated with PTEN mutations. In addition to the dysplastic gangliocytoma, the patient showed TDP43-pathology in the cortex and in the substantia nigra, and p62-positive/TDP43-negative inclusions in the cerebellar granule cells. His sister carried the same gene defect and showed similar type of TDP43/p62-pathology in her brain. Our findings confirm the clinical and pathological picture of C9orf mutation carriers is more heterogeneous than originally thought and warrant further studies on the possible involvement of PTEN pathway in the specific cerebellar granule cell pathology associated with C9orf expansion

Methods

Results

Conclusion