Evidence map›Paper›PMID 40498122›Full record

ArticleJournal of neurology2025

Burden of pathogenetic and likely pathogenetic variants in SPG7, SPG11 and AP4 genes in Amyotrophic Lateral Sclerosis. A case-control study.

Paolo Niccolò Doronzio, Serena Lattante, Daniela Bernardo, Agata Katia Patanella, Giulia Bisogni, Emiliana Meleo, Elda Del Giudice, Davide Colavito, Lucia Maria Porro, Eleonora Sabatelli and 4 more

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Article in Journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

14 authors.

Paolo Niccolò DoronzioDepartment of Life Sciences and Public Health, Section of Genomic Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Serena LattanteDepartment of Experimental Medicine, University of Salento, Lecce, Italy.
Daniela BernardoCentro Clinico NEMO. Fondazione Policlinico Gemelli IRCCS, Largo Gemelli, 8, 00168, Rome, Italy.
Agata Katia PatanellaCentro Clinico NEMO. Fondazione Policlinico Gemelli IRCCS, Largo Gemelli, 8, 00168, Rome, Italy.
Giulia BisogniCentro Clinico NEMO. Fondazione Policlinico Gemelli IRCCS, Largo Gemelli, 8, 00168, Rome, Italy.
Emiliana MeleoCentro Clinico NEMO. Fondazione Policlinico Gemelli IRCCS, Largo Gemelli, 8, 00168, Rome, Italy.
Elda Del GiudiceResearch & Innovation (R&I Genetics) srl, Padua, Italy.
Davide ColavitoResearch & Innovation (R&I Genetics) srl, Padua, Italy.
Lucia Maria PorroCentro Clinico NEMO. Fondazione Policlinico Gemelli IRCCS, Largo Gemelli, 8, 00168, Rome, Italy.
Eleonora SabatelliNeurologic Unit. Policlinico Casilino, Rome, Italy.
Amelia ConteCentro Clinico NEMO. Fondazione Policlinico Gemelli IRCCS, Largo Gemelli, 8, 00168, Rome, Italy.
Marcella ZollinoDepartment of Life Sciences and Public Health, Section of Genomic Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Mario SabatelliCentro Clinico NEMO. Fondazione Policlinico Gemelli IRCCS, Largo Gemelli, 8, 00168, Rome, Italy. mario.sabatelli@unicatt.it.ORCID http://orcid.org/0000-0001-6635-4985
Giuseppe MarangiDepartment of Life Sciences and Public Health, Section of Genomic Medicine, Catholic University of the Sacred Heart, Rome, Italy.

Funding

Catholic University of Sacred Hearth Linea D1
6 · The paper itself

Abstract

backgroundThere is evidence that some Hereditary Spastic Paraplegia (HSP) genes are linked to Amyotrophic Lateral Sclerosis (ALS). In particular, KIF5A and SPG11 genes, which cause two different forms of HSP, are also associated with adult-onset and Juvenile ALS, respectively.

objectivesTo study the frequencies of pathogenetic and likely pathogenetic variants in HSP genes in ALS patients and to determine whether they act as predisposing factors.

methodsWe analysed 72 HSP-associated genes in 1024 ALS and 44 Primary Lateral Sclerosis patients and applied customized ACMG criteria to identify pathogenic and likely pathogenic variants. Based on the frequency of identified variants, six genes, including SPG7, SPG11 and the four genes encoding the subunits of the AP4 adaptor protein, were selected for analysis in an additional cohort of 481 ALS patients. Overall results on 1549 patients were compared with 1138 controls.

resultsThe frequency of variants in SPG7 gene was 0.45% (7/1549) in patients vs 0.18% (2/1138) in controls (p = 0.19), in SPG11 was 0.77% (12/1549) in cases and 0.26% (3/1138) in controls (p = 0.06), in AP4 genes was 0.64% (10/1549) in patients and 0.26% (3/1138) in controls (p = 0.13). The total number of variants detected across SPG7, SPG11 and AP4 genes was statistically different between patients and controls (1.87% vs 0.7%; p = 0.006).

conclusionsWe found a significant enrichment of variants in a set of HSP genes, including SPG7, SPG11 and AP4 genes, in a large cohort of ALS patients, suggesting that they may act as predisposing factors for ALS.

Indexed as

Adaptor Protein Complex 4Amyotrophic Lateral SclerosisGenetic Predisposition to DiseaseProteinsAdultAgedATPases Associated with Diverse Cellular ActivitiesCase-Control StudiesFemaleGenetic VariationHumansMaleMetalloendopeptidasesMiddle AgedSpastic Paraplegia, HereditaryAdaptor Protein Complex 4ATPases Associated with Diverse Cellular ActivitiesMetalloendopeptidasesProteinsSPG11 protein, humanSPG7 protein, humanAmyotrophic lateral sclerosisAP4 complexHereditary spastic paraplegiaSPG11SPG7

Identifiers

PMID40498122

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.