Hereditary spastic paraplegia type 11 with a very late onset

Rubegni, Anna; Storti, Eugenia; Tessa, Alessandra; Federico, Antonio; Santorelli, Filippo M.

doi:10.1007/s00415-015-7854-9

Cited by 9 publications

(8 citation statements)

References 6 publications

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“…The disease usually starts in adolescence, and by the age of 25, most patients develop full clinical manifestations. However, our patients had adult-onset disease and a similar observation was described by other authors [ 24 , 25 ]. Interestingly, two Czech SPG11 patients with late-onset disease were compound heterozygotes for the c.5381T>C variant that was also described in our patients with late-adult onset [ 26 ].…”

Section: Discussionsupporting

confidence: 90%

Phenotypic and Genetic Heterogeneity of Adult Patients with Hereditary Spastic Paraplegia from Serbia

Perić

Marković

Candayan

et al. 2022

Cells

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Hereditary spastic paraplegia (HSP) is among the most genetically diverse of all monogenic diseases. The aim was to analyze the genetic causes of HSP among adult Serbian patients. The study comprised 74 patients from 65 families clinically diagnosed with HSP during a nine-year prospective period. A panel of thirteen genes was analyzed: L1CAM (SPG1), PLP1 (SPG2), ATL1 (SPG3A), SPAST (SPG4), CYP7B1 (SPG5A), SPG7 (SPG7), KIF5A (SPG10), SPG11 (SPG11), ZYFVE26 (SPG15), REEP1 (SPG31), ATP13A2 (SPG78), DYNC1H1, and BICD2 using a next generation sequencing-based technique. A copy number variation (CNV) test for SPAST, SPG7, and SPG11 was also performed. Twenty-three patients from 19 families (29.2%) had conclusive genetic findings, including 75.0% of families with autosomal dominant and 25.0% with autosomal recessive inheritance, and 15.7% of sporadic cases. Twelve families had mutations in the SPAST gene, usually with a pure HSP phenotype. Three sporadic patients had conclusive findings in the SPG11 gene. Two unrelated patients carried a homozygous pathogenic mutation c.233T>A (p.L78*) in SPG7 that is a founder Roma mutation. One patient had a heterozygous de novo variant in the KIF5A gene, and one had a compound heterozygous mutation in the ZYFVE26 gene. The combined genetic yield of our gene panel and CNV analysis for HSP was around 30%. Our findings broaden the knowledge on the genetic epidemiology of HSP, with implications for molecular diagnostics in this region.

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Section: Discussionsupporting

confidence: 90%

Phenotypic and Genetic Heterogeneity of Adult Patients with Hereditary Spastic Paraplegia from Serbia

Perić

Marković

Candayan

et al. 2022

Cells

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“…Missense mutations were found to be associated with earlier onset in SPG4 patients while the p.Ala510Val variant in SPG7 was found to be associated with a later disease onset and a more ataxic clinical presentation (Parodi et al, 2018b;Coarelli et al, 2019). Similarly, missense mutations in SPG11 are often associated with a later onset (Rubegni et al, 2015). Genetic modifiers have been reported to explain part of the variability in clinical presentation.…”

Section: Genetic Diagnosis: Approaches Yield and Gap In Genetic Etiologymentioning

confidence: 99%

Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview

Elsayed

Eltazi

Ahmed

et al. 2021

Front. Mol. Biosci.

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Hereditary spastic paraplegias (HSP) are a heterogeneous group of motor neurodegenerative disorders that have the core clinical presentation of pyramidal syndrome which starts typically in the lower limbs. They can present as pure or complex forms with all classical modes of monogenic inheritance reported. To date, there are more than 100 loci/88 spastic paraplegia genes (SPG) involved in the pathogenesis of HSP. New patterns of inheritance are being increasingly identified in this era of huge advances in genetic and functional studies. A wide range of clinical symptoms and signs are now reported to complicate HSP with increasing overall complexity of the clinical presentations considered as HSP. This is especially true with the emergence of multiple HSP phenotypes that are situated in the borderline zone with other neurogenetic disorders. The genetic diagnostic approaches and the utilized techniques leave a diagnostic gap of 25% in the best studies. In this review, we summarize the known types of HSP with special focus on those in which spasticity is the principal clinical phenotype (“SPGn” designation). We discuss their modes of inheritance, clinical phenotypes, underlying genetics, and molecular pathways, providing some observations about therapeutic opportunities gained from animal models and functional studies. This review may pave the way for more analytic approaches that take into consideration the overall picture of HSP. It will shed light on subtle associations that can explain the occurrence of the disease and allow a better understanding of its observed variations. This should help in the identification of future biomarkers, predictors of disease onset and progression, and treatments for both better functional outcomes and quality of life.

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“…As TCC is the major hallmark of patients with complicated HSP and typically associated with cognitive impairment, early and widespread involvement of cognitive functions across all domains is a well-known phenomenon in SPG11-related HSP-TCC [37]. However, there are still lots of late-onset cases without cognitive complaints, and potential mild cognitive de cits in some speci c domains of prefrontal functions may be easily neglected and inaccurately described by conventional MMSE, which is widely used for screening general cognitive decline or dementia, but inadequate for lack of prefrontal-related tasks [5][6][7]. Unlike MMSE, MoCA is designed to adding assessments or increasing di culties of prefrontal functions such as visuoexecution, abstraction, delayed recall and language, and widely used to evaluate mild cognitive impairment (MCI) in degenerative diseases [25].…”

Section: Discussionmentioning

confidence: 99%

“…and potential mild cognitive de cits in multiple domains may be easily neglected and inaccurately described by conventional Mini-Mental State Examination (MMSE) assessment [5][6][7].…”

mentioning

confidence: 99%

Mild Cognitive Impairment in novel SPG11 Mutation-Related Sporadic Hereditary Spastic Paraplegia with Thin Corpus Callosum

Yan

Duan

et al. 2020

Preprint

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Background: SPG11 mutation-related autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is the most common cause in complicated forms of HSP, usually presenting comprehensive mental retardation on early-onset stage preceding spastic paraplegias in childhood. However, there are still lots of sporadic late-onset HSP-TCC cases with negative family history, and potential mild cognitive deficits in multiple domains may be easily neglected and inaccurately described. Methods: In this study, we performed next generation sequencing in four sporadic late-onset patients with spastic paraplegia and thin corpus callosum (TCC), and combined Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to evaluate cognition of the patients. Results: By evolutionary conservation and structural modeling analysis, we have revealed 4 novel pathogenic SPG11 mutations, and firstly confirmed mild cognitive impairment (MCI) with normal MMSE scores (≥27) and decreased MoCA scores (<26) in these SPG11 mutation-related HSP-TCC patients, predominantly presenting impairment of visuoexecutive function, delayed recall, abstraction and language correlated with prefrontal deficits.Conclusions: The results expand the mutational spectrum of SPG11-associated HSP-TCC from sporadic cases, and confirm MCI characterized with dysfunction of prefrontal lobe in SPG11-related HSP-TCC, which should be paid more attention by neurologists.

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Hereditary spastic paraplegia type 11 with a very late onset

Cited by 9 publications

References 6 publications

Phenotypic and Genetic Heterogeneity of Adult Patients with Hereditary Spastic Paraplegia from Serbia

Phenotypic and Genetic Heterogeneity of Adult Patients with Hereditary Spastic Paraplegia from Serbia

Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview

Mild Cognitive Impairment in novel SPG11 Mutation-Related Sporadic Hereditary Spastic Paraplegia with Thin Corpus Callosum

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