Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms

Salinas, Sara; Proukakis, Christos; Crosby, Andrew H.; Warner, Thomas T.

doi:10.1016/s1474-4422(08)70258-8

Cited by 481 publications

(511 citation statements)

References 131 publications

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“…The corresponding proteins are often involved in intracellular trafficking or mitochondrial functions. 2,3 Clinically, one can distinguish between pure and complicated forms of HSP. 1,2 Pure forms consist of isolated pyramidal signs, such as spasticity, abnormal reflexes (brisk reflexes and Babinski sign) and motor deficit, often associated with sphincter disturbances and deep sensory loss.…”

Section: Introductionmentioning

confidence: 99%

“…2,3 Clinically, one can distinguish between pure and complicated forms of HSP. 1,2 Pure forms consist of isolated pyramidal signs, such as spasticity, abnormal reflexes (brisk reflexes and Babinski sign) and motor deficit, often associated with sphincter disturbances and deep sensory loss. In the complicated forms of HSP the disease is variably associated with numerous combinations of neurological and extraneurological signs, such as cerebellar ataxia, dysarthria, mental retardation, peripheral neuropathy, optic atrophy, retinitis pigmentosa and/or hearing loss, which may be accompanied by abnormal brain MRI (atrophy of the cortex, cerebellum or corpus callosum, white matter abnormalities, etc).…”

Section: Introductionmentioning

confidence: 99%

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KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: distinct phenotypes according to the nature of the mutations

et al. 2012

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The hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterised by progressive spasticity in the lower limbs. The nosology of autosomal recessive forms is complex as most mapped loci have been identified in only one or a few families and account for only a small percentage of patients. We used next-generation sequencing focused on the SPG30 chromosomal region on chromosome 2q37.3 in two patients from the original linked family. In addition, wide genome scan and candidate gene analysis were performed in a second family of Palestinian origin. We identified a single homozygous mutation, p.R350G, that was found to cosegregate with the disease in the SPG30 kindred and was absent in 970 control chromosomes while affecting a strongly conserved amino acid at the end of the motor domain of KIF1A. Homozygosity and linkage mapping followed by mutation screening of KIF1A allowed us to identify a second mutation, p.A255V, in the second family. Comparison of the clinical features with the nature of the mutations of all reported KIF1A families, including those reported recently with hereditary sensory and autonomic neuropathy, suggests phenotypegenotype correlations that may help to understand the mechanisms involved in motor neuron degeneration. We have shown that mutations in the KIF1A gene are responsible for SPG30 in two autosomal recessive HSP families. In published families, the nature of the KIF1A mutations seems to be of good predictor of the underlying phenotype and vice versa. INTRODUCTIONThe hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterised by progressive spasticity in the lower limbs. 1 The mode of inheritance may be autosomal dominant, autosomal recessive (ARHSP) or X-linked. More than 48 different loci (SPGn) have been mapped so far, and 23 responsible genes identified. The corresponding proteins are often involved in intracellular trafficking or mitochondrial functions. 2,3 Clinically, one can distinguish between pure and complicated forms of HSP. 1,2 Pure forms consist of isolated pyramidal signs, such as spasticity, abnormal reflexes (brisk reflexes and Babinski sign) and motor deficit, often associated with sphincter disturbances and deep sensory loss. In the complicated forms of HSP the disease is variably associated with numerous combinations of neurological and extraneurological signs, such as cerebellar ataxia, dysarthria, mental retardation, peripheral neuropathy, optic atrophy, retinitis pigmentosa and/or hearing loss, which may be accompanied by abnormal brain MRI (atrophy of the cortex, cerebellum or corpus callosum, white matter abnormalities, etc).Mutations in the KIF1A gene (MIM 601255) were very recently described in two different clinically and genetically heterogeneous groups of neurodegenerative diseases. 4,5 In hereditary sensory and autonomic neuropathy (HSAN), all patients from four families with different origins shared a common hom...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: distinct phenotypes according to the nature of the mutations

et al. 2012

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“…The formation of different isoenzymes may therefore explain different pathogenic effects of mutations in m-AAA protease subunits. Loss of function of paraplegin (encoded by the SPG7 gene) causes an autosomal recessive form of hereditary spastic paraplegia (HSP; Casari et al, 1998), a neurodegenerative disorder characterized by retrograde degeneration of cortical motor axons and peripheral sensory neurons (Rugarli and Langer, 2006;Salinas et al, 2008). Mutations in Afg3l2, on the other hand, impair axonal development in mice (Maltecca et al, 2008) and have been associated recently with the degeneration of Purkinje cells in autosomal dominant spinocerebellar ataxia (SCA) type 28 (Cagnoli et al, 2008;DiBella et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Autocatalytic Processing of m-AAA Protease Subunits in Mitochondria

Koppen

Bonn

Ehses

et al. 2009

MBoC

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“…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%

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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Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms

Cited by 481 publications

References 131 publications

KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: distinct phenotypes according to the nature of the mutations

KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: distinct phenotypes according to the nature of the mutations

Autocatalytic Processing of m-AAA Protease Subunits in Mitochondria

Clinical features and management of hereditary spastic paraplegia

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