ABSTRACT
Background: The World Health Organization (WHO) 2016 classification incorporated molecular subtyping in glioma, highlighting the diagnostic and prognostic significance. The study aims to determine the isocitrate dehydrogenase (IDH-1) gene, α-thalassemia/mental retardation syndrome X-linked (ATRX) gene, and tumor suppressor gene-53 (p53) mutation in glioma and their correlation with various clinical and radiological parameters.Methods: In this prospective observational study, histopathological slides of glioma (2017-2018), were analyzed for IDH-1, ATRX and p53 mutations and their correlation with various clinical and radiological parameters.Results: IDH-1 mutation was found in 48 (38.7%), ATRX loss in 38 (30.6%) and p53 mutation in 40 (32.5%) patients. The expression of IDH-1 was significantly higher (43.7%) in adults; however, no significant difference was seen with gender. Also 51.2% of patients, who presented with seizures, showed IDH-1 expression; and 27.7% of patients, who had neurological deficit also showed IDH-1 expression. IDH-1 expression was high in glioma located at insula (73.3%) and parietal lobe (71.4%); while ATRX loss was seen in glioma located at insula (80%). Intraventricular glioma characteristically lacks all three markers: IDH-1 expression, p53 overexpression and ATRX loss. IDH-1 expression and p53 overexpression was seen mainly in diffuse fibrillary astrocytoma, oligodendroglioma, anaplastic astrocytoma and glioblastoma.Conclusions: Molecular subtyping is of paramount importance in glioma management. IDH-1 mutation is commonly observed in adults and patients presenting with seizures. The duration of symptoms correlates with IDH-1 and ATRX mutations. Hypothalamic tumors lack all three mutations.
ABSTRACT
Monomelic amyotrophy (MA), also known as Hirayama disease, occurs mainly in young men and manifests as weakness and wasting of the muscles of the distal upper limbs. Here, we sought to identify a genetic basis for MA. Given the predominance of MA in males, we focused on candidate neurological disease genes located on the X chromosome, selecting two X-linked candidate genes, androgen receptor (AR) and ubiquitin-like modifier activating enzyme 1 (UBA1). Screening for genetic variants using patients' genomic DNA revealed three known genetic variants in the coding region of the AR gene: one nonsynonymous single-nucleotide polymorphism (SNP; rs78686797) encoding Leu57Gln, and two variants of polymorphic trinucleotide repeat segments that encode polyglutamine (CAG repeat; rs5902610) and polyglycine (GGC repeat; rs3138869) tracts. Notably, the Leu57Gln polymorphism was found in two patients with MA from 24 MA patients, whereas no variants were found in 142 healthy male controls. However, the numbers of CAG and GGC repeats in the AR gene were within the normal range. These data suggest that the Leu57Gln polymorphism encoded by the X-linked AR gene may contribute to the development of MA.