Search results for " onset"

Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis.

2006

Variation in major histocompatibility complex genes on chromosome 6p21.3, specifically the human leukocyte antigen HLA-DR2 or DRB1*1501-DQB1*0602 extended haplotype, confers risk for multiple sclerosis (MS). Previous studies of DRB1 variation and both MS susceptibility and phenotypic expression have lacked statistical power to detect modest genotypic influences, and have demonstrated conflicting results. Results derived from analyses of 1339 MS families indicate DRB1 variation influences MS susceptibility in a complex manner. DRB1*15 was strongly associated in families (P=7.8x10(-31)), and a dominant DRB1*15 dose effect was confirmed (OR=7.5, 95% CI=4.4-13.0, P<0.0001). A modest dose effect…

Rational design of allosteric modulators of the aromatase enzyme: An unprecedented therapeutic strategy to fight breast cancer.

2019

Estrogens play a key role in cellular proliferation of estrogen-receptor-positive (ER+) breast cancers (BCs). Suppression of estrogen production by competitive inhibitors of the enzyme aromatase (AIs) is currently one of the most effective therapies against ER + BC. Yet, the development of acquired resistance, after prolonged treatments with AIs, represents a clinical major concern. Serendipitous findings indicate that aromatase may be non-competitively inhibited by clinically employed drugs and/or industrial chemicals. Here, by performing in silico screening on two putative allosteric sites, molecular dynamics and free energy simulations, supported by enzymatic and cell-based assays, we id…

Predictors of definite Multiple Sclerosis in patients with pediatric onset first demyelinating clinical attack

2014

A Novel CCT5 Missense Variant Associated with Early Onset Motor Neuropathy

2020

Diseases associated with acquired or genetic defects in members of the chaperoning system (CS) are increasingly found and have been collectively termed chaperonopathies. Illustrative instances of genetic chaperonopathies involve the genes for chaperonins of Groups I (e.g., Heat shock protein 60, Hsp60) and II (e.g., Chaperonin Containing T-Complex polypeptide 1, CCT). Examples of the former are hypomyelinating leukodystrophy 4 (HLD4 or MitCHAP60) and hereditary spastic paraplegia (SPG13). A distal sensory mutilating neuropathy has been linked to a mutation [p.(His147Arg)] in subunit 5 of the CCT5 gene. Here, we describe a new possibly pathogenic variant [p.(Leu224Val)] of the same subunit b…

Reveglucosidase alfa (BMN 701), a GILT-tagged recombinant human acid alpha glucosidase (rhGAA), evaluation in late-onset Pompe disease: Preliminary c…

2015

Preliminary clinical efficacy and safety of BMN 701, GILT-tagged recombinant human acid alpha glucosidase (rhGAA), in late-onset Pompe disease: resul…

2014

Metachromatic leukodystrophy (MLD) is a lysosomal disorder that results from the deficiency of the lysosomal enzyme arylsulfatase A. It is characterized by motor and developmental regression, seizures, deafness, blindness, dementia and premature death. There are three types of onsets: late infantile, juvenile, and adult. We performed a retrospective chart review of 71 patients (47 infantile, 23 juvenile) evaluated at the Program for Study of Neurodevelopment in Rare Disorders (NDRD) between January 2000 and August 2013. The patients were evaluated prospectively using a standardized protocol. The purpose of the study is to describe the natural course of the disease. In 31 patients only a bas…

Early onset ONJ in patient treated with denosumab and bevacizumab: case report

2016

Benign and severe early-life seizures: a round in the first year of life

2018

Abstract Background At the onset, differentiation between abnormal non-epileptic movements, and epileptic seizures presenting in early life is difficult as is clinical diagnosis and prognostic evaluation of the various seizure disorders presenting at this age. Seizures starting in the first year of life including the neonatal period might have a favorable course, such as in infants presenting with benign familial neonatal epilepsy, febrile seizures simplex or acute symptomatic seizures. However, in some cases, the onset of seizures at birth or in the first months of life have a dramatic evolution with severe cerebral impairment. Seizure disorders starting in early life include the “epilepti…

Ataxin-1 and ataxin-2 intermediate-length PolyQ expansions in amyotrophic lateral sclerosis.

2012

ABSTRACT Objective: Recent evidence suggests that intermediate-length polyglutamine (PolyQ) expansions in the ataxin-2 ( ATXN-2 ) gene are a risk factor for amyotrophic lateral sclerosis (ALS). This work was undertaken with the aim to investigate the frequency of ataxin-1 ( ATXN-1 ) and ATXN-2 PolyQ expansions in a cohort of patients with sporadic ALS (sALS) and patients with familial ALS (fALS) from southern Italy. Methods: We assessed the PolyQ lengths of ATXN-1 and ATXN-2 in 405 patients with sALS, 13 patients with fALS, and 296 unrelated controls without history of neurodegenerative disorders. Results: We found significantly higher intermediate PolyQ expansions ≥32 for ATXN-1 alleles an…

Changes over three decades in outcome and the prognostic influence of age-at-diagnosis in young patients with neuroblastoma: a report from the Intern…

2011

Abstract Purpose Increasing age has been an adverse risk factor in children with neuroblastoma (NB) since the 1970’s, with a 12-month age-at-diagnosis cut-off for treatment stratification. Over the last 30 years, treatment intensity for children >12 months with advanced-stage disease has increased; to investigate if this strategy has improved outcome and/or reduced the prognostic influence of age, we analysed the International Neuroblastoma Risk Group (INRG) database. Patients and methods Data from 11,037 children with NB (1974–2002) from Australia, Europe, Japan, North America. Cox modelling of event-free survival (EFS) tested if the era and prognostic significance of age-of-diagnosis, adj…