A new locus (SPG47) maps to 1p13.2–1p12 in an Arabic family with complicated autosomal recessive hereditary spastic paraplegia and thin corpus callosum

Blumkin, Lubov; Lerman‐Sagie, Tally; Lev, Dorit; Yosovich, Keren; Leshinsky‐Silver, Esther

doi:10.1016/j.jns.2011.03.011

Cited by 32 publications

(23 citation statements)

References 18 publications

(36 reference statements)

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“…We describe a novel AP4B1 frameshift mutation [c.664delC) responsible for autosomal recessive hereditary spastic paraplegia with intellectual disability and thin corpus callosum in the original SPG47 family [2]. The notion that AP4B1 is indeed the SPG47 gene is confirmed by a recent report of Abou Jamra et al [7], who described a second family with a different AP4B1 mutation (c.487_488insTAT) but with a similar phenotype.…”

Section: Discussionsupporting

confidence: 57%

“…The patients and their MRIs were described in detail in our original article [2]. Exome sequencing: to find the disease causing mutation within the candidate region on chromosome 1, we performed exome sequencing on both affected siblings.…”

Section: Methodsmentioning

confidence: 99%

“…We recently reported a new type of hereditary spastic paraplegia (SPG47) in a consanguineous Arabic family and mapped it to chromosome 1p13.2-1p12 [2]. The daughter initially presented with severe developmental delay and hypotonia and later developed progressive spastic paraparesis and convulsions.…”

Section: Introductionmentioning

confidence: 99%

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Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47)

et al. 2012

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We recently identified a new locus for spastic paraplegia type 47 (SPG47) in a consanguineous Arabic family with two affected siblings with progressive spastic paraparesis,intellectual disability, seizures, periventricular white matter changes and thin corpus callosum. Using exome sequencing, we now identified a novel AP4B1 frameshift mutation (c.664delC) in this family. This mutation was homozygous in both affected siblings and heterozygous in both parents. The mutant allele was absent in 316 Caucasian and 200 ethnically matched control chromosomes. We propose that AP4B1 mutations cause SPG47 and should be considered in early onset spastic paraplegia with intellectual disability.

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Section: Discussionsupporting

confidence: 57%

Section: Methodsmentioning

confidence: 99%

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Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47)

et al. 2012

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“…7 Abou Jamra et al 1 and Najmabadi et al 8 described homozygous mutations of AP4B1 (MIM 614066), AP4S1 (MIM 614067), AP4E1, and AP4M1 in individuals with severe ID, growth retardation, stereotypic laughter, progressive spasticity, and inability to walk as the core phenotype. Two Arabic siblings with hereditary spastic paraplegia (HSP), ID, and seizures 9 were found to carry the homozygous c.664delC mutation in AP4B1. 10 Thinning of the corpus callosum has been proposed to be a key feature of the AP-4-associated HSP.…”

Section: Introductionmentioning

confidence: 99%

An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome

et al. 2014

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The recently proposed adaptor protein 4 (AP-4) deficiency syndrome comprises a group of congenital neurological disorders characterized by severe intellectual disability (ID), delayed or absent speech, hereditary spastic paraplegia, and growth retardation. AP-4 is a heterotetrameric protein complex with important functions in vesicle trafficking. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been reported in patients with the AP-4 deficiency phenotype. We describe two siblings from a non-consanguineous couple who presented with severe ID, absent speech, microcephaly, growth retardation, and progressive spastic tetraplegia. Whole-exome sequencing in the two patients identified the novel homozygous 2-bp deletion c.1160_1161delCA (p.(Thr387Argfs*30)) in AP4B1. Sanger sequencing confirmed the mutation in the siblings and revealed it in the heterozygous state in both parents. The AP4B1-associated phenotype has previously been assigned to spastic paraplegia-47. Identification of a novel AP4B1 alteration in two patients with clinical manifestations highly similar to other individuals with mutations affecting one of the four AP-4 subunits further supports the observation that loss of AP-4 assembly or functionality underlies the common clinical features in these patients and underscores the existence of the clinically recognizable AP-4 deficiency syndrome.

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“…These are the areas with higher expression of spastacsin in the brain and this pattern helps us to understand why movement disorders are so frequent in SPG 11 42 . Despite this, one must consider that thinning of the corpus callosum is not SPG11-specific, because it is also found in other HSPs such as: SPG 4,7,15,18,21,46,47,49 and 54 3,11,21,44,45,46 . Progressive hydrocephalus due to aqueductal stenosis is highly suggestive of X-linked SPG1.…”

Section: Neuroimaging Studiesmentioning

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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A new locus (SPG47) maps to 1p13.2–1p12 in an Arabic family with complicated autosomal recessive hereditary spastic paraplegia and thin corpus callosum

Cited by 32 publications

References 18 publications

Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47)

Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47)

An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome

Clinical features and management of hereditary spastic paraplegia

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