Clinical and Genetic Features of Patients with Juvenile Amyotrophic Lateral Sclerosis with Fused in Sarcoma (FUS) Mutation

Yu, Xiaohong; Zhao, Zhe; Shen, Hongrui; Qi, Bing; Li, Nan; Hu, Jing

doi:10.12659/msm.913724

Cited by 12 publications

(11 citation statements)

References 23 publications

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“…JALS is inherited in an autosomal-recessive pattern involving ALS2 , SPG11 , and SIGMAR1 , while the SETX, UBQLN2, and FUS mutations are described as an underlying cause of an autosomal-dominant form of JALS [ 28 ]. Clinical manifestation reflects the degeneration of both upper motor neurons and lower motor neurons causing weakness of the lower limbs, spasticity of facial muscles, uncontrolled laughter, dysarthria, bladder dysfunction, sensory disturbances, and, in rare cases, mental retardation and scoliosis [ 29 , 30 ]. Death usually occurs from respiratory failure between 7 and 84 months after onset [ 25 , 28 , 30 , 31 , 32 , 33 , 34 , 35 ].…”

Section: Macroscopic Level: Clinical Features Of Iahsp and Other Als2-related Pathologiesmentioning

confidence: 99%

ALS2-Related Motor Neuron Diseases: From Symptoms to Molecules

Miceli

Exertier

Cavaglià

et al. 2022

Biology

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Infantile-onset Ascending Hereditary Spastic Paralysis, Juvenile Primary Lateral Sclerosis and Juvenile Amyotrophic Lateral Sclerosis are all motor neuron diseases related to mutations on the ALS2 gene, encoding for a 1657 amino acids protein named Alsin. This ~185 kDa multi-domain protein is ubiquitously expressed in various human tissues, mostly in the brain and the spinal cord. Several investigations have indicated how mutations within Alsin’s structured domains may be responsible for the alteration of Alsin’s native oligomerization state or Alsin’s propensity to interact with protein partners. In this review paper, we propose a description of differences and similarities characterizing the above-mentioned ALS2-related rare neurodegenerative disorders, pointing attention to the effects of ALS2 mutation from molecule to organ and at the system level. Known cases were collected through a literature review and rationalized to deeply elucidate the neurodegenerative clinical outcomes as consequences of ALS2 mutations.

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Section: Macroscopic Level: Clinical Features Of Iahsp and Other Als2-related Pathologiesmentioning

confidence: 99%

ALS2-Related Motor Neuron Diseases: From Symptoms to Molecules

Miceli

Exertier

Cavaglià

et al. 2022

Biology

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“…In addition to the aggressive and early onset of these cases, some are also associated with learning difficulties and mental retardation. 2,4,5,[10][11][12] However, other atypical features for ALS are rare. Myoclonus with generalized spikewave discharges have been recently described in a boy with FUS-ALS at 17 years of age.…”

Section: Pediatric Amyotrophic Lateral Sclerosismentioning

confidence: 99%

“…37 Also, a phenomenon of anticipation have also been described in a juvenile case and his affected mother. 12…”

Section: Mutation-directed Aggressivity Of Fus Casesmentioning

confidence: 99%

The Occurrence of FUS Mutations in Pediatric Amyotrophic Lateral Sclerosis: A Case Report and Review of the Literature

et al. 2020

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Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease affecting both upper and lower motor neurons and leading to progressive paralysis. Most cases are sporadic, and the symptoms generally begin in the sixth or seventh decade. Juvenile ALS appears in a rare subgroup of patients with onset before the age of 25 years old. Contrary to the classical adult phenotype where 90% of cases are sporadic, most cases of juvenile ALS are caused by a genetic mutation in either SOD1 (superoxide dismutase one), SETX (senataxin), or FUS (fused in sarcoma). In the pediatric population, ALS is more infrequent and rarely considered in the differential diagnosis. There are few reports of ALS in children. Here, we describe a 14-year-old boy with a very fast progressing classical ALS phenotype and tremor caused by a c.1554_1557delACAG mutation in FUS. Our review of the literature advocates that pediatric ALS is highly suggestive of FUS mutations and that gene should be tested in children presenting with symptoms of ALS. The children with FUS-related ALS may have no family history and present initially with learning disabilities, tremor, and mild motor developmental delay.

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“…3 , 4 The most common histologic subtypes of STS are undifferentiated sarcoma (US), liposarcoma (LPS), synovial sarcoma (SS) and leiomyosarcoma (LMS), which are associated with different molecular characteristics and behavior features. 5 , 6 According to the National Comprehensive Cancer Network guidelines of STS, surgical resection is the curable treatment option. However, other treatment regimens for STS are extremely scarce and the prognosis remains dismal.…”

Section: Introductionmentioning

confidence: 99%

The landscape of gene mutations and clinical significance of tumor mutation burden in patients with soft tissue sarcoma who underwent surgical resection and received conventional adjuvant therapy

Zhao

et al. 2020

Int J Biol Markers

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Background The aim of this study was to evaluate the landscape of gene mutations and the clinical significance of tumor mutation burden (TMB) in patients with soft tissue sarcoma who underwent surgical resection and received conventional adjuvant therapy. Methods A total of 68 patients with soft tissue sarcoma were included. Postoperative tumor tissue specimens from the patients were collected for DNA extraction. Targeted next-generation sequencing of cancer-relevant genes was performed for the detection of gene mutations and the analysis of TMB. Univariate analysis between TMB status and prognosis was carried out using the Kaplan–Meier survival analysis, and multivariate analysis was adjusted by the Cox regression model. Results No specific genetic mutations associated with soft tissue sarcoma were found. The mutation frequency of TP53, PIK3C2G, NCOR1, and KRAS of the 68 patients with soft tissue sarcoma were observed in 19 cases (27.94%), 15 cases (22.06%), 14 cases (20.59%), and 14 cases (20.59%), respectively. With regard to the analysis of TMB, the overall TMB of the 68 patients with soft tissue sarcoma was relatively low (median: 2.05 per Mb (range: 0∼15.5 per Mb)). Subsequently, TMB status was divided into TMB-Low and TMB-Middle according to the median TMB. Patients with TMB-Low and TMB-Middle were 37 cases (54.41%) and 31 cases (45.59%), respectively. Overall survival analysis indicated that the median overall survival of patients with TMB-Low and TMB-Middle was not reached, and 4.5 years, respectively ( P=0.015). Conclusion This study characterizes the genetic background of patients with STS soft tissue sarcoma. The TMB was of clinical significance for patients with soft tissue sarcoma who underwent surgical resection and received conventional adjuvant therapy.

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Clinical and Genetic Features of Patients with Juvenile Amyotrophic Lateral Sclerosis with Fused in Sarcoma (FUS) Mutation

Cited by 12 publications

References 23 publications

ALS2-Related Motor Neuron Diseases: From Symptoms to Molecules

ALS2-Related Motor Neuron Diseases: From Symptoms to Molecules

The Occurrence of FUS Mutations in Pediatric Amyotrophic Lateral Sclerosis: A Case Report and Review of the Literature

The landscape of gene mutations and clinical significance of tumor mutation burden in patients with soft tissue sarcoma who underwent surgical resection and received conventional adjuvant therapy

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