Linkage of Familial Amyotrophic Lateral Sclerosis With Frontotemporal Dementia to Chromosome 9q21-q22

TLDR

Amyotrophic lateral sclerosis is a progressive motor neuron disease that usually presents as a pure motor syndrome but can co‑occur with frontotemporal dementia, and while most cases are sporadic, about 10 % are familial and overlap syndromes have been reported, with the majority of familial cases having unknown causes and ~25 % due to SOD1 mutations. The study sought to uncover the genetic basis of familial ALS cases that co‑manifest with frontotemporal dementia. Researchers performed a genome‑wide linkage analysis on 16 pedigrees to locate disease‑associated loci. They identified a novel chromosomal locus linked to a subtype of ALS that is frequently accompanied by frontotemporal dementia.

Abstract

MYOTROPHIC LATERAL SCLErosis (ALS) is a progressive disease characterized by degeneration of both upper and lower motor neurons.Typically, it develops as a pure motor syndrome.However, in rare cases (probably Ͻ5%) ALS arises concurrently with other neurodegenerative phenotypes such as frontotemporal dementia (FTD) 1-3 or other extrapyramidal or cortical and subcortical syndromes. 1While most cases of ALS occur in unrelated individuals (sporadic ALS), familial inheritance is observed in about 10% of cases (FALS). 4nalogously, cases of neurodegenerative overlap syndromes may also arise on a familial basis.Thus, pedigrees have been reported with ALS-FTD 1,5 and with combinations of ALS, Parkinson disease (PD), and dementia. 4,6,7[8][9][10][11] The cause of most cases of ALS is unknown.About 25% of FALS cases are caused by defects in the gene encoding copper-zinc cytosolic superoxide dismutase (SOD1). 12,13To define the pathogenesis of other FALS cases, we conducted genome-wide linkage analysis involving 16 pedigrees.In the course of this screening, we identified a new locus for a subtype of ALS in which, in the same family and often in the same individuals, ALS is conjoined with FTD.