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Prion diseases are a group of fatal neurodegenerative disorders that occur in inherited, acquired and sporadic forms, a characteristic that makes them unique. Herein, we review the literature to update the current knowledge of these diseases, with particular emphasis on the inherited forms. The PRNP gene is located on chromosome 20 and contains two exons and one intron. It encodes the prion protein (PrPc) that comprises 253 aminoacids and exhibits a polymorphism on the codon 129 (valine or metionine) that can modify the disease phenotype. The hallmark of prion diseases is the misfolding of the prion protein observed in the brain of affected individuals (prion-only hypothesis). Creutzfeldt- Jackob disease (CJD) can be sporadic or iatrogenic and there is a new variant. Dominantly inherited forms include familial CJD, Gerstmann-Straussler-Scheinker disease, and fatal familial insomnia that arise from germline mutations in the PRNP gene. There are three types of pathogenic PRNP mutations: point mutations leading to an aminoacid substitution or premature stop codon, and insertion of additional octapeptide repeats. Predictive diagnosis is possible in all inherited prion diseases, resulting in ethical issues. Even though prion diseases have been known for several years they are an enigma in biology, thus a better understanding of the underlying mechanisms that generate them is needed. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a heterogeneus and complex disease. Three genes that cause autosomal dominant AD have been identified and include APP (amyloid precursor protein) gene on chromosome 21, the PS1 (presenil 1) gene on chromosome 14, and the PS2 (presenilin 2) gene on chromosome 1 an additional gene, the Apo-E (apolipoprotein) gene on chromosome 19 has been described as a risk factor for developing AD because of an increased prevalence of the Apo-E e4 allele in patients with AD. Another genes associated to the disease had been found in chromosome X and 12, in chromosome 12 a deletion in the alpha-2 macroglobulin gen had been also described as a risk factor. Recently a novel type of mutation in messenger RNA of β amyloid precursor protein and ubiquitin- B was discovered in AD patients. Mutations in mitochondrial DNA may represent also a primary etiologic event directly participating in a cascade of events that results in AD. [ABSTRACT FROM AUTHOR]

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Background and Purpose: Creutzfeldt-Jakob disease (CJD) is a rare, rapidly fatal neurodegenerative disorder. The gold standard test for a positive diagnosis of definite CJD is histopathological confirmation, usually post-mortem; however, an autopsy study is not always feasible in all health settings., Materials and Methods: We performed a cross-sectional analysis of a retrospectively enrolled cohort of patients with suspected prion disease between 2008 and 2019. Only patients with complete medical histories who fulfilled a diagnostic checklist were enrolled. The magnetic resonance imaging (MRI) sequences (T2-FLAIR and DWI) were analyzed, and the apparent diffusion coefficients (ADCs) were calculated for five regions of interest (ROIs) in each cerebral hemisphere., Results: In total, 72 MRI scans were post-processed. The series included 47 cases of CJD, including 25 genetic and 22 sporadic cases, in addition to 25 age-paired controls with non-prion encephalopathies. The neostriatum showed the most significant difference in ADC values (×10 -3 mm 2 /s) at 0.5946 in the left anterior putamen vs. 0.8644 in the control encephalopathies (p < 0.001; 95% confidence interval: 0.5751-0.6142 vs. 0.7812-0.9476), while the other ROIs also showed significant differences. The best cut-off value to differentiate CJD from other encephalopathies was identified as 0.65×10 -3 mm 2 /s, with no significant differences in this coefficient between sporadic and genetic cases., Conclusions: Quantitative ADC measurements made in the basal ganglia seem to be the most useful ante-mortem diagnostic tool for differentiating CJD from non-prion encephalopathies when cerebrospinal fluid real-time quaking-induced conversion or other specific misfolded protein detection tests are inaccessible., (Copyright © 2024 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)

Leukodystrophies comprise a spectrum of genetic disorders affecting white matter (WM) formation in the central nervous system (CNS), of which vanishing white matter disease (VWMD) is one. VWMD presents with progressive neurological deterioration and a variety of manifestations. Ovarioleukodystrophy, a subtype of VWMD, exhibits a distinctive clinical profile encompassing both CNS WM alterations and ovarian dysfunction. Variants in genes of the eukaryotic translation initiation factor 2B (EIF2B) complex affect the full form and are implicated in VWMD, including ovarioleukodystrophy. This work aimed to systematically review all published cases of ovarioleukodystrophy associated with variants in the EIF2B1-5 gene complex based on the first case identified in a Mexican population. We performed a systematic review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines of published cases of ovarioleukodystrophy associated with the EIF2B gene complex, including a newly identified case from Mexico. We identified 207 publications using PUBMED, SCOPUS, and PMC databases. One hundred fifty-one publications were eliminated due to duplicates, titles, abstracts, or other reasons, while 56 publications were revised, of which 29 were eliminated because they dealt with other genes or non-human research, and 27 reports were assessed for eligibility. Finally, 14 reports describing ovarian involvement, neuroimaging, and molecular variants were included. Our review identified 20 cases worldwide, with a median age of onset of 19 years. Clinical features included WM involvement, ovarian abnormalities, gait disturbances, epilepsy, cognitive and language impairment, and other neurological manifestations. Neuroimaging showed characteristic WM changes, highlighting the importance of MRI in diagnosis. Missense variants predominated among the identified genetic mutations, especially in the EIF2B4 and EIF2B5 genes. Ovarioleukodystrophy is an ultra-rare disorder with a wide range of clinical manifestations and ovarian changes. Gynecological evaluation is crucial in suspected cases of ovarioleukodystrophy, as ovarian manifestations may precede neurological symptoms. The role of MRI is crucial in the diagnostic approach to this entity. Continued collaborative efforts are essential to elucidate genotype-phenotype correlations, improve clinical management, and promote therapeutic advances for this rare disorder., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Escobar-Pacheco et al.)

Background: Parkin mutations in patients with early-onset Parkinson's disease (EOPD) are estimated to occur in 49% of familial cases and 18% of sporadic cases., Methods: We analyzed the entire sequence-coding region and dosage mutations of parkin in 63 Mexican-mestizo EOPD patients and 120 controls., Results: Parkin mutations were present in 34 patients (54.0%). Exon rearrangements, predominantly spanning exons 9 and 12 (31.7% and 19.0%, respectively) were present in 32 patients, with 17.5% carrying simple heterozygous and 25.4% carrying compound heterozygous parkin mutations., Conclusions: A higher frequency of parkin exon rearrangements than of sequence mutations was observed. Patients with parkin exons 9 and 12 rearrangements showed a later age at onset than did cases with other regions affected (40.3 ± 4.5 vs 30.1 ± 8.8; P = .005), suggesting a mutational hot spot in the etiology of Mexican-mestizo patients with EOPD. To our knowledge, this study represents the largest sampling of Mexican-mestizo patients with EOPD cases for which parkin sequence and dosage alterations were analyzed. ., (Copyright © 2012 Movement Disorder Society.)

The presence of different ethnic groups in Mexico may give rise to genetic diversity between the native Indian population and the Mestizos. It is therefore of medical and anthropological interest to analyze the genotypes of disease-associated loci, such as polymorphism in the apolipoprotein E gene, whose 4/4 allele increases the risk of Alzheimer's disease and coronary heart disease in other populations. We studied a Nahua Indian-population in the State of Morelos (Santo Domingo Ocotitlan). The ABO blood type of all individuals was determined and compared with the findings of other Nahua group from the State of Puebla. Without statistical significant differences in O, A and AB groups between both populations (p > 0.05). The allelic and genotypic frequency of apolipoprotein E was similar to that observed in other Mexican indian (Mazatecans, Mayans) and Mestizo populations, however there was a statistically significant difference when the results were compared to the allelic frequencies of other Amerinds: The Cayapa (Ecuador) for the epsilon 3 and epsilon 4 alleles (p < 0.002); the Nuuk (Greenland) for epsilon 3 and epsilon 4 alleles (p < 0.0001 and p < 0.002 respectively); and the Ammssalik (Greenland) for both alleles with p < 0.0001 and p = 0.04 respectively. In the case of the genotypes, there was statistically significant difference for the 4/3 genotypes, but a non significant difference for the 4/4 genotype. This is a descriptive study which contributes to the knowledge of the genetic structure of Mexican population.