Reevaluation of a large family defines a new locus for X-linked recessive pure spastic paraplegia (SPG34) on chromosome Xq25

Macedo‐Souza, Lúcia Inês; Kok, Fernando; Santos, Silvana; Licinio, Luciana; Lezirovitz, Karina; Nascimento, Rafaella Maria Pessutti; Bueno, Clarissa; Martyn, Marcília Lima; Leão, Emília K. E. A.; Zatz, Mayana

doi:10.1007/s10048-008-0130-8

Cited by 20 publications

(7 citation statements)

References 6 publications

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“…Clinical presentation: affected patients present with a pure form of SPG. SPG34 has been reported in a single family so far [131]. Female carriers are usually unaffected.…”

Section: Spg34mentioning

confidence: 95%

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

Finsterer

Löscher

Quasthoff

et al. 2012

Journal of the Neurological Sciences

246

211

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“…Clinical presentation: affected patients present with a pure form of SPG. SPG34 has been reported in a single family so far [131]. Female carriers are usually unaffected.…”

Section: Spg34mentioning

confidence: 95%

“…Aetiology: the mutated gene has not been identified yet but linkage-analysis located it to Xq25 [131].…”

Section: Spg34mentioning

confidence: 98%

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

Finsterer

Löscher

Quasthoff

et al. 2012

Journal of the Neurological Sciences

246

211

View full text Add to dashboard Cite

“…Gene identity at the SPG16 (Steinmuller et al, 1997) and SPG34 (Macedo-Souza et al, 2008) loci are unknown (details in Tables 1 and 2).…”

Section: Xlhspmentioning

confidence: 99%

Hereditary spastic paraplegia: Clinical-genetic characteristics and evolving molecular mechanisms

Giudice

Lombardi

Santorelli

et al. 2014

Experimental Neurology

285

264

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Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurological disorders characterized by pathophysiologic hallmark of length-dependent distal axonal degeneration of the corticospinal tracts. The prominent features of this pathological condition are progressive spasticity and weakness of the lower limbs. To date, 72 spastic gait disease-loci and 55 spastic paraplegia genes (SPGs) have been identified. All modes of inheritance (autosomal dominant, autosomal recessive, and X-linked) have been described. Recently, a late onset spastic gait disorder with maternal trait of inheritance has been reported, as well as mutations in genes not yet classified as spastic gait disease. Several cellular processes are involved in its pathogenesis, such as membrane and axonal transport, endoplasmic reticulum membrane modeling and shaping, mitochondrial function, DNA repair, autophagy, and abnormalities in lipid metabolism and myelination processes. Moreover, recent evidences have been found about the impairment of endosome membrane trafficking in vesicle formation and about the involvement of oxidative stress and mtDNA polymorphisms in the onset of the disease. Interactome networks have been postulated by bioinformatics and biological analyses of spastic paraplegia genes, which would contribute to the development of new therapeutic approaches.

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“…Furthermore, HSP can be inherited as an autosomal-dominant (AD-HSP), autosomal-recessive (AR-HSP), or rarely, as an X-linked (X-HSP) trait [8]. The number of different loci associated with HSP includes 18 for AD-HSP, 22 for AR-HSP, and 4 for X-linked HSP [7,9-11]. …”

Section: Introductionmentioning

confidence: 99%

Unique spectrum of SPAST variants in Estonian HSP patients: presence of benign missense changes but lack of exonic rearrangements

et al. 2010

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BackgroundHereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous disorder that can be an autosomal-dominant, autosomal-recessive, or X-linked disease. The most common autosomal-dominant form of the disease derives from mutations in the SPAST gene.MethodsThe aim of this study was to analyze 49 patients diagnosed with HSP from the Estonian population for sequence variants of the SPAST gene and to describe the associated phenotypes. Healthy control individuals (n = 100) with no family history of HSP were also analyzed. All patient samples were screened using denaturing high performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA) assay. Samples with abnormal DHPLC and MLPA profiles were sequenced, with the same regions sequenced in control samples.ResultsSequence variants of SPAST were identified in 19/49 HSP patients (38.8%), twelve among them had pathogenic mutations. Within the latter group there was one sporadic case. Eight patients had pure, and four - complex HSP. The twelve variants were identified: seven pathogenic (c.1174-1G>C, c.1185delA, c.1276C>T, c.1352_1356delGAGAA, c.1378C>A, c.1518_1519insTC, c.1841_1842insA) and five non-pathogenic (c.131C>T, c.484G>A, c.685A>G, c.1245+202delG, c.1245+215G>C). Only 2 of these mutations had previously been described (c.131C>T, c.1245+202delG). Three mutations, c.1174-1G>C, c.1276 C>T, c.1378C>A, showed intrafamilial segregation.ConclusionThis study identified new variants of the SPAST gene which included benign missense variants and short insertions/deletions. No large rearrangements were found. Based on these data, 7 new pathogenic variants of HSP are associated with clinical phenotypes.

show abstract

Reevaluation of a large family defines a new locus for X-linked recessive pure spastic paraplegia (SPG34) on chromosome Xq25

Cited by 20 publications

References 6 publications

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

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

Hereditary spastic paraplegia: Clinical-genetic characteristics and evolving molecular mechanisms

Unique spectrum of SPAST variants in Estonian HSP patients: presence of benign missense changes but lack of exonic rearrangements

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