‘Pure’ and ‘Complicated’ Forms of Hereditary Spastic Paraplegia Presenting in Childhood

Appleton, Richard; Farrell, Kevin; Dunn, Henry G.

doi:10.1111/j.1469-8749.1991.tb14881.x

Cited by 25 publications

(14 citation statements)

References 25 publications

(22 reference statements)

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“…Furthermore, the protein complexes crosslinked to protrudin at site R330, denoted by asterisks in Supplementary Fig. 3E, were also analyzed by LC-MS. KIF5, a known protrudin interactor, was identified, which is consistent with previous results that protrudin perform its interaction with KIF5 through the NH2-terminal portion of the FYVE domain (amino acids 274–361)25. It is indicated that we could obtain different interacting proteins by incorporating DiZPK into different sites of protrudin.…”

Section: Resultssupporting

confidence: 90%

Fatty acid synthase cooperates with protrudin to facilitate membrane outgrowth of cellular protrusions

Zhang¹,

Lü²,

Su³

et al. 2017

Sci Rep

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Cellular protrusion formation capacity is a key feature of developing neurons and many eukaryotic cells. However, the mechanisms underlying membrane growth in protrusion formation are largely unclear. In this study, photo-reactive unnatural amino acid 3-(3-methyl-3H-diazirin-3-yl)-propamino-carbonyl-Nε-l-lysine was incorporated by a genetic code expansion strategy into protrudin, a protein localized in acidic endosomes and in the endoplasmic reticulum, that induces cellular protrusion and neurite formation. The modified protrudin was used for covalent trapping of protrudin-interacting proteins in living cells. Fatty acid synthase (FASN), which synthesizes free fatty acids, was identified to transiently interact with protrudin. Further characterization revealed a unique cooperation mechanism in which protrudin cooperates with FASN to facilitate cellular protrusion formation. This work reveals a novel mechanism involved in protrusion formation that is dependent on transient interaction between FASN and protrudin, and establishes a creative strategy to investigate transient protein-protein interactions in mammalian cells.

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Section: Resultssupporting

confidence: 90%

Fatty acid synthase cooperates with protrudin to facilitate membrane outgrowth of cellular protrusions

Zhang¹,

Lü²,

Su³

et al. 2017

Sci Rep

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“…The majority (81.1%) of the children in our study had complicated HSP which also comprised 65% of cases in an earlier study. 13 In another series of 72 children, autosomal recessive HSP was seen in 17%, and 25% of these cases had complicated HSP. 6 This wide variability in the pure and complicated forms in our study may be related to the particular cohort of patients, the geographical location, patient genetics and the possibility of consanguinity in the population.…”

Section: Discussionmentioning

confidence: 94%

Clinical Spectrum of Hereditary Spastic Paraplegia in Children : A Study of 74 Cases = الطيف السريري للشلل السفلي التشنجي الوراثي في الأطفال : دراسة 74 حالة

Koul¹,

Al-Murshedi²,

Al-Azri³

et al. 2013

SQUMJ

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abstract:Objectives: The aim of the study was to explore the spectrum of hereditary spastic paraplegia (HSP) in children in Oman. Methods: This retrospective study was carried out between January 1994 and August 2011 on children with delayed development, gait disorders and motor handicaps, with signs of symmetrical pyramidal tract involvement. A detailed perinatal and family history, including the age of onset of symptoms, was recorded. The children were labelled as having either the pure or complicated form of HSP based on the established diagnostic criteria. In families with more than one affected child, parents and all other siblings were also examined. Results: Within the study, 74 children from 31 families were diagnosed with HSP. Parental consanguinity was seen in 91% of cases, with 44 children (59.4%) experiencing onset of the disease under one year of age. Complicated HSP was the most common type, seen in 81.1%. Speech involvement, mental retardation, and epilepsy were the most common associated abnormalities. Nonspecific white matter changes and corpus callosum abnormalities were noted in 24.3% of cases on magnetic resonance imaging. Conclusion: The study described clinical features of 74 children with HSP. Autosomal recessive complicated HSP was seen in 81.1% of cases. Keywords

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“…6 In our HSP database, an early age at symptom onset (prior to age 18) was found in 72 of 175 (41%) patients, with a heterogeneous genetic background: 47 of 72 (65%) autosomal dominant cases, 12 of 72 (17%) autosomal recessive cases, and 13 of 72 (18%) sporadic cases. Gait difficulties were the presenting symptom in 81%, with a mean age of 8 years.…”

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confidence: 90%

Child Neurology: Hereditary spastic paraplegia in children

Bot¹,

Warrenburg²,

Kremer³

et al. 2010

Neurology

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Because the medical literature on hereditary spastic paraplegia (HSP) is dominated by descriptions of adult case series, there is less emphasis on the genetic evaluation in suspected pediatric cases of HSP. The differential diagnosis of progressive spastic paraplegia strongly depends on the age at onset, as well as the accompanying clinical features, possible abnormalities on MRI, and family history. In order to develop a rational diagnostic strategy for pediatric HSP cases, we performed a literature search focusing on presenting signs and symptoms, age at onset, and genotype. We present a case of a young boy with a REEP1 (SPG31) mutation.CASE REPORT A 4-year-old boy presented with progressive walking difficulties from the time he started walking at the age of 12 to 13 months. His family history was significant for minimal gait abnormalities with onset after age 35, occurring in the patient's mother, maternal grandfather, and maternal aunt; none of them had ever sought medical attention. Neurologic examination revealed a mildly spastic gait and marked lower limb hyperreflexia with bilateral Babinski signs present. Vibration perception was reduced at the ankles. Neurologic examination of the patient's mother and maternal aunt revealed subtle gait abnormalities with bilateral Babinski signs present.MRI of the brain and spinal cord and general metabolic screening revealed no abnormalities. Diagnostic genetic testing in both the patient and his mother revealed a pathogenic mutation (c.417 ϩ 1 GϾT) in REEP1 (SPG31) which causes a pure HSP. Mutations in ATL1 (SPG3A) and SPAST (SPG4) had previously been excluded. DISCUSSION HSP is a genetically and clinically heterogeneous group of disorders in which the main clinical feature is progressive lower limb spasticity secondary to pyramidal tract dysfunction. HSP is classified as pure if neurologic signs are limited to the lower limbs (although urinary urgency and mild impairment of vibration perception in the distal lower extremities may occur). In contrast, complicated forms of HSP display additional neurologic and MRI abnormalities such as ataxia, more significant peripheral neuropathy, mental retardation, or a thin corpus callosum. HSP may be inherited as an autosomal dominant, autosomal recessive, or X-linked disease. Over 40 loci and nearly 20 genes have already been identified.1 Autosomal dominant transmission is observed in 70% to 80% of all cases and typically results in pure HSP. Spastic paraplegia is a common problem in the daily practice of pediatric neurologists, generally caused by acquired brain disorders such as perinatal asphyxia or infections early in life resulting in cerebral palsy. In addition, there is a long list of more rare disorders to consider when confronted with spastic paraplegia including structural, infectious, demyelinating, and metabolic disorders (table). 3 Only in a small minority of cases does HSP underlie the spastic syndrome. Many patients with childhood-onset HSP are mistakenly diagnosed with cerebral palsy. 4,5 In children with spasti...

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‘Pure’ and ‘Complicated’ Forms of Hereditary Spastic Paraplegia Presenting in Childhood

Cited by 25 publications

References 25 publications

Fatty acid synthase cooperates with protrudin to facilitate membrane outgrowth of cellular protrusions

Fatty acid synthase cooperates with protrudin to facilitate membrane outgrowth of cellular protrusions

Clinical Spectrum of Hereditary Spastic Paraplegia in Children : A Study of 74 Cases = الطيف السريري للشلل السفلي التشنجي الوراثي في الأطفال : دراسة 74 حالة

Child Neurology: Hereditary spastic paraplegia in children

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