CASE PRESENTATION: We present a consanguineous Qatari family with two brothers, 9 and 3 years, who displayed a characteristic phenotype of early onset and markedly-severe spasticity with tiptoe walking, delayed dysarthric speech, persistent truncal hypotonia [read.qxmd.com]

The present family emphasizes SPG45 with NT5C2 mutations as a member of the TCC-SPG subgroup. [bmcmedgenet.biomedcentral.com]

A novel, 1954-bp homozygous deletion at the NT5C2 locus involving the entire coding exon 11 was identified to be present in both sequenced, affected siblings. [cyberleninka.org]

Despite recent pioneering improvements in intensified combination chemotherapy, 20% of pediatric and 50% of adult ALL patients present with primary drug-resistant leukemia or develop relapse. [academiccommons.columbia.edu]

• Disability

  JOINT SET BOYS CAP - BLUE LILY - SOFT PINK S 00021-PU Your cart Cart is empty View cart Checkout Orders history Newsletter Registration About Schulte Fact Sheets Links Authentication Username Password Log in Register Recover password If Javascript is disabled [gerrys.com.au]

  For a subset of patients (n = 65), disability was evaluated using the SPATAX-EUROSPA disability score, ranging from 0 (no disability) to 7 (severe disability/confined to bed). [ng.neurology.org]

  Some SPG45 patients manifest mental retardation, contractures and learning disability. Acronym SPG45 Keywords Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. [uniprot.org]

• Weakness

  Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. [uniprot.org]

  See also: Leg: Leg weakness, leg sensations, leg paresthesias, leg tingling, leg numbness Knee: knee weakness, knee sensations, knee paresthesias, knee tingling, knee numbness Foot: foot weakness, foot sensations, foot paresthesias, foot tingling, foot [familydiagnosis.com]

• Falling

  Falls - risk assessment A fall is defined as an unintentional/unexpected loss of balance resulting in coming to rest on the floor, the ground, or an object below knee level. [evidence.nhs.uk]

  Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below. [invitae.com]

  MyBioSource and its authorized distributors reserve the right to refuse to process any order where we reasonably believe that the intended use will fall outside of our acceptable guidelines. [mybiosource.com]

  KCNA2 encephalopathy falls into two big groups, the “A phenotype” due to activating mutations in the voltage sensor and “B phenotype” due to dominant-negative loss of function mutations outside of the voltage sensor. [epilepsygenetics.net]

  […] paresthesias, hand tingling, hand numbness Finger: finger weakness, finger sensations, finger paresthesias, finger tingling, finger numbness • • • Sleep paralysis : Sleep paralysis This is a temporary inability to move or speak that occurs when waking up or falling [familydiagnosis.com]

• Short Stature

  stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia Spinocerebellar ataxia type 12 Typical nemaline myopathy X-linked agammaglobulinemia X-linked hyper-IgM syndrome [csbg.cnb.csic.es]

  Most common symptoms of SPASTIC PARAPLEGIA 45, AUTOSOMAL RECESSIVE; SPG45 Autosomal recessive inheritance Intellectual disability Global developmental delay Short stature Microcephaly More info about SPASTIC PARAPLEGIA 45, AUTOSOMAL RECESSIVE; SPG45 SOURCES [mendelian.co]

  22-33 Gait + + Primary Increased Upward - Normal (or not 3a years abnormalities optical done) atrophy, myopia, congenital nystagmus 14 months - 3-33 Gait + + Primary Increased Upward Aggressiveness, Thin corpus 4 4 years, years abnormalities optical short [cyberleninka.org]

  stature, craniofacial dysmorphism, and congenital heart defects B3GAT3 Muscular dystrophy-dystroglycanopathy FKTN Myelodysplastic syndrome, somatic TET2 Myoclonus Dystonie SGCE Myopathy due to myoadenylate deaminase deficiency AMPD1 Myotonia Congenita [meduniwien.ac.at]

  The gene locations are in the format: chromosome - arm (short or p: long or q) - band number. These designations are for the human genes only. The locations may (and probably will) vary in other organisms. [en.wikipedia.org]

• Pallor

  The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. [genecards.org]

• Muscle Spasm

  Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. [uniprot.org]

• Muscle Cramp

  cramps 611773 120130 Autosomal dominant COL4A1 13q34 {Hemorrhage, intracerebral, susceptibility to} 614519 120130 COL4A1 13q34 Porencephaly 1 175780 120130 Autosomal dominant COL4A1 13q34 Brain small vessel disease with or without ocular anomalies 607595 [mnglabs.com]

• Muscle Spasticity

  A recessive form of spastic paraplegia with distal muscle wasting. Arch Neurol 1967, 16 :473–485. PubMed Google Scholar 55. [link.springer.com]

• Suggestibility

  Investigators found evidence to suggest that mutations in the NT5C2 gene make leukemic cells resistant to a common chemotherapy drug but vulnerable to a class of drugs called IMPDH inhibitors. [hematologytimes.com]

  A clinical diagnosis suggestive of complex hereditary spastic paraplegia (HSP) was set after the family had the second affected child. [read.qxmd.com]

  These results suggest that ALL relapse-associated NT5C2 mutations likely confer not only increase in endogenous nucleotidase activity but also novel enzymatic functions that specially affect thiopurine metabolism. [ash.confex.com]

  These results suggest that mutations in NT5C2 are associated with the outgrowth of drug-resistant clones in ALL. publication date March 2013 published in Nature Genetics Journal Research keywords Academic Article Identity Language eng PubMed Central ID [vivo.med.cornell.edu]

• Incontinence

  In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Some SPG45 patients manifest mental retardation, contractures and learning disability. [uniprot.org]

  […] palsy ( facial paralysis ) Carpal tunnel syndrome (hand paralysis; wrist paralysis; finger paralysis) Cubital tunnel syndrome Footdrop (foot paralysis; foot weakness ) Wristdrop Cauda equina syndrome (lower body paralysis, autonomic nerve paralysis, incontinence [familydiagnosis.com]

• Spastic Paraplegia

  Autosomal Recessive Spastic Paraplegia Type 45 Is also known as autosomal recessive spastic paraplegia type 65, spg45, spg65. Currently, we don't have any information about doctors, researches or researchers related to this disease. [mendelian.co]

  Email: [email protected] Search for more papers by this author First published: 08 September 2017 Cited by: 4 Abstract SPG45 is a rare form of autosomal recessive spastic paraplegia associated with mental retardation. [onlinelibrary.wiley.com]

  spastic paraplegia Pure or complex autosomal recessive spastic paraplegia Pure or complex hereditary spastic paraplegia Spastic paraplegia type 2 Spastic paraplegia type 7 X-linked complex spastic paraplegia X-linked pure spastic paraplegia X-linked spastic [se-atlas.de]

  Home Science NGS Panel – Genetic Testing for Spastic Paraplegia Hereditary Spastic Paraplegia (HSP), Spastic paraplegia, SPG, Familial Spastic Paraplegia, Hereditary Spastic Paraparesis, Strumpell-Lorrain Syndrome Hereditary Spastic Paraplegia (HSP) autosomal [centogene.com]

  Genes and mapped phenotypes Gene ID: 100322879, updated on 8-Apr-2017 Summary Official Symbol SPG45 provided by HGNC Official Full Name spastic paraplegia 45 (autosomal recessive) provided by HGNC Primary source HGNC:HGNC:35431 See related MIM:613162 [ncbi.nlm.nih.gov]

• Spastic Gait

  gait Commonly - More than 50% cases Lower limb spasticity Not very common - Between 30% and 50% cases Abnormal cerebellum morphology Commonly - More than 50% cases Paraplegia Not very common - Between 30% and 50% cases Spastic paraplegia And 18 more [mendelian.co]

  Hereditary spastic paraplegia ( HSP ) is a group of inherited diseases whose main feature is a progressive gait disorder. [en.wikipedia.org]

  Diagnosis of SPG is established by the following clinical features 1, 2 : Typical clinical symptoms of spastic gait impairment and neurologic findings of spastic weakness, hyperreflexia, typically associated with bilateral extensor plantar responses A [centogene.com]

  Coordination was normal and their gait was spastic. Although patients were not cooperative for sensory testing, no prominent sensory abnormality was detected. A summary of the clinical details can be found in Table 1. [cyberleninka.org]

• Lower Extremity Spasticity

  Spastic paraplegia 4, autosomal dominant Get Update Overview The hereditary spastic paraplegias (SPG, HSP) are a group of clinically and genetically diverse inherited disorders characterized predominantly by progressive lower extremity spasticity and [diseaseinfosearch.org]

  […] to slowly progressive lower extremity spasticity and weakness. [research.unipd.it]

  […] characterized by progressive, usually severe, lower extremity spasticity and weakness. [flybase.org]

  “Complicated” HSP is the diagnosis given to an individual who suffers with lower extremity spasticity along with such neurological problems as peripheral neuropathy, seizures, ataxia, optic neuropathy, retinopathy, dementia, mental retardation, and deafness [medschool.lsuhsc.edu]

• Myoclonus

  […] dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation Costello syndrome Developmental malformations - deafness - dystonia Ewing sarcoma Extraskeletal Ewing sarcoma Extraskeletal myxoid chondrosarcoma FTH1-related iron overload Familial cortical myoclonus [csbg.cnb.csic.es]

  Exostosen, multiple hereditäre Osteochondrome, HME, HMO EXT1, EXT2 Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects B3GAT3 Muscular dystrophy-dystroglycanopathy FKTN Myelodysplastic syndrome, somatic TET2 Myoclonus [meduniwien.ac.at]

  Parkinsonism ( PD, Postencephalitic, NMS ) · PKAN · Tauopathy ( PSP ) · Striatonigral degeneration · Hemiballismus · HD · OA Dyskinesia : Dystonia ( Status dystonicus, Spasmodic torticollis, Meige's, Blepharospasm ) · Athetosis, Chorea ( Choreoathetosis ) · Myoclonus [psychology.wikia.com]

• Babinski Sign

  Babinski sign was present and there was preserved abdominal-cutaneous reflex, but neither tremor nor dystonic features were observed. Coordination was normal and their gait was spastic. [cyberleninka.org]

In this context, we will perform detailed structure-function analysis of NT5C2 mutant proteins to guide the development of new therapies for the treatment of relapse and refractory ALL. [grantome.com]

Surprisingly, mutation of NT5C2 was not associated with response to relapse treatment. Response was assessed by histological examination and by PCR-based sensitive detection of minimal residual disease at different time points during treatment. [bloodjournal.org]

It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice . [uniprot.org]

Treatment of refractory and relapsed ALL has remained a significant clinical challenge with survival rates following relapse of only 40%, highlighting the need to understand the mechanisms which drive drug resistance and relapse of ALL. [academiccommons.columbia.edu]

This research proposal follows on our detailed structural and functional characterization of activated mutant forms of NT5C2 identified in relapsed ALL and seeks to set the basis for the development of mutant specific NT5C2 inhibitors for the treatment [alexslemonade.org]

[…] related to NT5C2 gene prognosis reporting PUBMED functional study NT5C2 differentiation "Diverse regulations also occurred with proteins in ...... " 15378696 Pubmed reporting Reported miRNA regulation of NT5C2 gastric cancer No result found. gene prognosis [cis.hku.hk]

Abstract Relapsed acute lymphoblastic leukaemia (ALL) is associated with resistance to chemotherapy and poor prognosis. [psychology.as.uky.edu]

Overview MeSH Major 5'-Nucleotidase Precursor Cell Lymphoblastic Leukemia-Lymphoma abstract Relapsed childhood acute lymphoblastic leukemia (ALL) carries a poor prognosis, despite intensive retreatment, owing to intrinsic drug resistance. [vivo.med.cornell.edu]

Recommend to your librarian Relapsed childhood acute lymphoblastic leukemia (ALL) carries a poor prognosis, despite intensive retreatment, owing to intrinsic drug resistance. The biological pathways that mediate resistance are unknown. [f1000.com]

Jude Children's Research Hospital, Memphis, TN Background Relapse remains as a formidable challenge for acute lymphoblastic leukemia (ALL), particularly because it is associated with dramatic drug resistance and thus dismal prognosis. [ash.confex.com]

Risch N et al. (1999) A genomic screen of autism: evidence for a multilocus etiology. [^] 26. [moldiag.com]

The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. [genecards.org]

Tijana Copf, Impairments in dendrite morphogenesis as etiology for neurodevelopmental disorders and implications for therapeutic treatments, Neuroscience & Biobehavioral Reviews, 10.1016/j.neubiorev.2016.04.008, 68, (946-978), (2016). [doi.org]

Consequently, they are often approached together in epidemiological studies. [karger.com]

Relevant External Links for SPG11 Genetic Association Database (GAD) SPG11 Human Genome Epidemiology (HuGE) Navigator SPG11 Atlas of Genetics and Cytogenetics in Oncology and Haematology: SPG11 No data available for Genatlas for SPG11 Gene Mutations in [genecards.org]

Jorde LB et al. (1990) The UCLA-University of Utah epidemiologic survey of autism: genealogical analysis of familial aggregation. [^] 6. Abramson RK et al. (1989) Elevated blood serotonin in autistic probands and their first-degree relatives. [^] 7. [moldiag.com]

The majority of individuals with HSP have a normal life expectancy. [16] Epidemiology [ edit ] Worldwide, the prevalence of all hereditary spastic paraplegias combined is estimated to be 2 to 6 in 100,000 people. [31] A Norwegian study of more than 2.5 [en.wikipedia.org]

Ishiura, Yuji Takahashi, Toshihiro Hayashi, Kayoko Saito, Hirokazu Furuya, Mitsunori Watanabe, Miho Murata, Mikiya Suzuki, Akira Sugiura, Setsu Sawai, Kazumoto Shibuya, Naohisa Ueda, Yaeko Ichikawa, Ichiro Kanazawa, Jun Goto and Shoji Tsuji, Molecular epidemiology [doi.org]

Pathophysiology [ edit ] The major feature of HSP is a length dependent axonal degeneration. [21] These include the crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis. [en.wikipedia.org]

Neuroglial interactions mediated by purinergic signalling in the pathophysiology of CNS disorders. Semin Cell Dev Biol. 2011;22:252–9. View Article PubMed Google Scholar Inoue K. Microglial Activation by Purines and Pyrimidines. [bmcmedgenet.biomedcentral.com]

TSL:5 NT5C2-205 ENST00000452156.5 856 265aa ENSP00000396468 - Q5JUV4 - 3' truncation in transcript evidence prevents annotation of the end of the CDS. [ensembl.org]

These compounds are useful tools in basic biomedical research and may be further developed for the treatment, prevention, or diagnosis of disease. [leibniz-fmp.de]

For long term storage store at -20C in small aliquots to prevent freeze-thaw cycles. Concentration: Approximately 0.5mg/ml. Actual concentration varies with each lot. [avivasysbio.com]

Incorporation of 5’-nucleotidase inhibitors targeting NT5C2 to initial therapy regimens or to salvage regimens at the time of relapse, or greater use of anti-tumor agents that are not affected by changes in this metabolic pathway, may prevent drug resistance [hematology.org]

[…] specificity and selectivity for mutant NT5C2, while our novel Nt5c2 R367Q knock-in mouse model will serve as a platform for the pre-clinical testing of both NT5C2 inhibitors and alternative compounds selective for Nt5c2-mutant leukemias which can be used for prevention [academiccommons.columbia.edu]