Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance

Finsterer, Josef; Löscher, Wolfgang N.; Quasthoff, Stefan; Wanschitz, Julia; Auer‐Grumbach, Michaela; Stevanin, Giovanni

doi:10.1016/j.jns.2012.03.025

Cited by 253 publications

(243 citation statements)

References 156 publications

(318 reference statements)

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“…SPG3A (ATL1) alone accounts for~10% of AD HSP. 8 On the contrary, AR HSP predominates in highly consanguineous communities. 7,9,10 Thin corpus callosum-associated HSP (TCC-HSP) represents a distinct subgroup accounting for approximately one-third of all AR HSP.…”

Section: Introductionmentioning

confidence: 99%

Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan

et al. 2016

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Hereditary spastic paraplegias (HSP) are the second most common type of motor neuron disease recognized worldwide. We investigated a total of 25 consanguineous families from Sudan. We used next-generation sequencing to screen 74 HSPrelated genes in 23 families. Linkage analysis and candidate gene sequencing was performed in two other families. We established a genetic diagnosis in six families with autosomal recessive HSP (SPG11 in three families and TFG/SPG57, SACS and ALS2 in one family each). A heterozygous mutation in a gene involved in an autosomal dominant HSP (ATL1/SPG3A) was also identified in one additional family. Six out of seven identified variants were novel. The c.64C4T (p.(Arg22Trp)) TFG/SPG57 variant (PB1 domain) is the second identified that underlies HSP, and we demonstrated its impact on TFG oligomerization in vitro. Patients did not present with visual impairment as observed in a previously reported SPG57 family (c.316C4T (p.(Arg106Cys)) in coiled-coil domain), suggesting unique contributions of the PB1 and coiled-coil domains in TFG complex formation/function and a possible phenotype correlation to variant location. Some families manifested marked phenotypic variations implying the possibility of modifier factors complicated by high inbreeding. Finally, additional genetic heterogeneity is expected in HSP Sudanese families. The remaining families might unravel new genes or uncommon modes of inheritance.

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Section: Introductionmentioning

confidence: 99%

Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan

et al. 2016

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“…They may segregate as an autosomal dominant, an autosomal recessive, X-linked or mitochondrial trait 1 . To date, there are up to 60 genetic types described 7 .…”

Section: Classificationmentioning

confidence: 99%

“…X-linked forms may present either as pure or complicated HSP. This distinction is clinically useful, but is not always found in genotypephenotype correlation studies 1 .…”

Section: Classificationmentioning

confidence: 99%

“…Disproportionate spasticity in contrast with mild weakness is a hallmark of this disorder. Mild reduction of vibration sense, or other sensory abnormalities together with urinary symptoms are frequent even in pure forms 1 . Complicated HSP comprise a large number of abnormalities such as ataxia, peripheral neuropathy, amyotrophy, seizures, movement disorders, cognitive impairment, retinopathy, optic atrophy, deafness and others 29,30 .…”

Section: Diagnosismentioning

confidence: 99%

“…In recent years, several genes and loci associated to HSP have been mapped 1,7 . On clinical grounds, these findings helped neurologists to perform more accurate and earlier diagnoses, as well as a sounder genetic counseling.…”

Section: Introductionmentioning

confidence: 99%

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Clinical features and management of hereditary spastic paraplegia

Faber

Servelhere

Martínez

et al. 2014

Arq. Neuro-Psiquiatr.

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Hereditary spastic paraplegia (HSP) is a group of genetically-determined disorders characterized by progressive spasticity and weakness of lower limbs. An apparently sporadic case of adult-onset spastic paraplegia is a frequent clinical problem and a significant proportion of cases are likely to be of genetic origin. HSP is clinically divided into pure and complicated forms. The later present with a wide range of additional neurological and systemic features. To date, there are up to 60 genetic subtypes described. All modes of monogenic inheritance have been described: autosomal dominant, autosomal recessive, X-linked and mitochondrial traits. Recent advances point to abnormal axonal transport as a key mechanism leading to the degeneration of the long motor neuron axons in the central nervous system in HSP. In this review we aim to address recent advances in the field, placing emphasis on key diagnostic features that will help practicing neurologists to identify and manage these conditions. Keywords: hereditary spastic paraplegia, spastic paraplegia, muscle spasticity, genetics, mutation. RESUMOParaplegias espásticas hereditárias (PEH) constituem um grupo de desordens geneticamente determinadas caracterizadas por espasticidade e paraparesia de progressão insidiosa. Paraplegia espástica aparentemente esporádica de início no adulto constitui problema frequente na prática neurológica. Evidências recentes sugerem que uma proporção significativa destes casos é geneticamente determinada. O grupo das PEH é dividido clinicamente em formas puras e complicadas de acordo com a concomitância de outras manifestações clinicas e neurológicas. Até o momento 60 tipos genéticos foram identificados. Todos os modos de herança monogênica já foram descritos: autossômica dominante, autossômica recessiva, ligada ao X e mitocondrial. Avanços recentes indicam que alterações do transporte axonal estão implicadas na degeneração dos longos axônios motores no sistema nervoso central na PEH. Nesta revisão abordamos recentes avanços na área com ênfase nos aspectos clínicos chave que ajudam o neurologista geral no diagnóstico e manejo correto deste grupo de doenças.Palavras-chave: paraplegia espástica hereditária, paraplegia espástica, espasticidade muscular, genética, mutação.

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