ALS with variable phenotypes in a six-generation family caused by leu144phe mutation in the SOD1 gene

Masè, Giovanni; Ros, Silvia Algaba; Gemma, Andrea; Bonfigli, L.; Carraro, Nicola; Cazzato, Giuseppe; Rolfo, Michela; Zanconati, Fabrizio; Sepčić, Juraj; Jurjević, Ante; Pirulli, Doroti; Boniotto, Michele; Zezlina, Silvia; Crovella, Sérgio; Amoroso, Antonio

doi:10.1016/s0022-510x(01)00625-6

Cited by 39 publications

(21 citation statements)

References 27 publications

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“…For instance, the most common familial variant (type 1 fALS associated with SOD1 mutations) shows significant phenotypic variability with respect to sites of onset and rates of disease progression, some of which is predicted by specific point mutations (Andersen et al 1997). When present, however, the frontotemporal syndrome associated with SOD1 mutations tends to be consistent with ALSbi (Masè et al 2001;Battistini et al 2005;Wicks et al 2009). A frontotemporal dementia with Parkinsonism and amyotrophy is linked to the microtubule associated tau protein at 17q21-22 (Hulette et al 1999;Lynch et al 1994).…”

Section: Clinical and Genetic Featuresmentioning

confidence: 99%

The Frontotemporal Syndromes of ALS. Clinicopathological Correlates

Strong

Yang

2011

J Mol Neurosci

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Amyotrophic lateral sclerosis (ALS) is increasingly recognized to be a syndromic disorder in which the degeneration of motor neurons is frequently accompanied by a range of syndromes reflective of frontotemporal dysfunction, including a behavioural or cognitive syndrome, a dysexecutive syndrome or a frontotemporal dementia. Both sporadic and familial variants of ALS can be affected. The anatomic substrate of each is a frontotemporal lobar degeneration (FTLD) characterized by superficial linear spongiosus, atrophy and neuronal loss, and both astrocytic and neuronal deposition of TDP-43 as pathological inclusions. Largely unrecognized however is the extent of alterations in tau protein metabolism, particularly in cognitively impaired patients (ALSci). This includes hyper-phosphorylation (pThr(175)) and tau phosphatase resistance, increased fibril formation ex vivo of tau isolated from ALSci and tau immunoreactive aggregates in neurons, dystrophic neurites and astrocytes. In this article, we will review the contemporary clinical, genetic and neuropathological characteristics of the frontotemporal syndromes of ALS and propose that as opposed to being a FTLD in which TDP-43 is the primary disease protein (FTLD-TDP) and that the frontotemporal syndromes of ALS represent a hybrid of both TDP-43 and tau pathology.

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Section: Clinical and Genetic Featuresmentioning

confidence: 99%

The Frontotemporal Syndromes of ALS. Clinicopathological Correlates

Strong

Yang

2011

J Mol Neurosci

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“…SOD1-linked polymorphic markers were analysed in the propositus, and compared with those from an affected subject and a healthy subject, both from the Istro-Rumanian FALS with the same SOD1 mutation. 4 As shown in Table 2, for each of the six markers examined the propositus shares at least one identical allele with the affected subject of the Istro-Rumanian FALS. The propositus and the healthy subject from the above family carry different alleles for almost all markers analysed (data not shown).…”

Section: Structural Analysismentioning

confidence: 99%

“…To date, this mutation has been described only in families with Istro-Rumanian, Yugoslavian and Croatian origin (http://www.alsod.org). 4 INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurological disease. Mutations of the Cu/Zn superoxide dismutase gene (SOD1) are responsible for 20% of autosomal dominant familial ALS (FALS).…”

Section: Introductionmentioning

confidence: 99%

An Italian dominant FALS Leu144Phe SOD1 mutation: genotype‐phenotype correlation

Ferrera

Caponnetto

Marini³

et al. 2003

Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders

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“…Within the FALS subgroup, approximately 20 % of patients carry a mutation in the gene for copper-zinc superoxide dismutase, SOD1 (SOD1 FALS) [40,41]. A disease-causing SOD1 mutation represents the only genetic test available for clinical screening of familial ALS; despite this there is an almost total absence of reports of cognitive dysfunction amongst SOD1 FALS patients in the literature [10,24]. A recent study specifically assessed cognitive function in FALS patients and found no differences on cognitive tests between sporadic and familial patients; however, only one of their 37 participants tested positive for SOD1 [49].…”

mentioning

confidence: 99%