The rs3857059 variant of the SNCA gene is associated with Parkinson's disease in Mexican Mestizos.

Among the candidate genes for Parkinson's disease (PD), SNCA has replicated association in different populations. Besides other known mutations in the SNCA gene, the rs3857059 variant has also been linked to various neurodegenerative disorders. Therefore, the aim of the present study was to search for association of this variant and sporadic PD in Mexican Mestizo patients. A case-control study was performed including 241 individuals, 106 patients, and 135 healthy controls. Genotyping was performed using real-time PCR. The rs3857059 variant demonstrated an association with PD in Mexican Mestizos (OR = 2.40, CI, 1.1 to 5.1, p = 0.02) under the recessive model. In addition, a gender effect was found for the GG genotype in females (OR = 1.31, CI, 1.01 to 1.7, p = 0.037). This is the first study to confirm an association of the rs3857059 variant with PD and also to show a gender effect. Our data contribute to the elucidation of the link between rs3857059 and susceptibility to PD observed in the Mexican Mestizo population.

The rs3857059 variant of the SNCA gene is associated with Parkinson's disease in Mexican Mestizos / A variante rs3857059 do gene SNCA é associada à doença de Parkinson em mestiços mexicanos

ABSTRACT Among the candidate genes for Parkinson’s disease (PD), SNCA has replicated association in different populations. Besides other known mutations in the SNCA gene, the rs3857059 variant has also been linked to various neurodegenerative disorders. Therefore, the aim of the present study was to search for association of this variant and sporadic PD in Mexican Mestizo patients. A case-control study was performed including 241 individuals, 106 patients, and 135 healthy controls. Genotyping was performed using real-time PCR. The rs3857059 variant demonstrated an association with PD in Mexican Mestizos (OR = 2.40, CI, 1.1 to 5.1, p = 0.02) under the recessive model. In addition, a gender effect was found for the GG genotype in females (OR = 1.31, CI, 1.01 to 1.7, p = 0.037). This is the first study to confirm an association of the rs3857059 variant with PD and also to show a gender effect. Our data contribute to the elucidation of the link between rs3857059 and susceptibility to PD observed in the Mexican Mestizo population.

RESUMO Entre genes candidatos para a doença de Parkinson (PD), SNCA foi replicado em diferentes populações. Além de outras mutações conhecidas no gene SNCA, a variante rs3857059 também tem sido associada a várias doenças neurodegenerativas. Portanto, o objetivo do presente estudo foi o de procurar variante de associação e PD esporádica em pacientes mestiços mexicanos. Um estudo de caso-controle foi executado, incluindo 241 indivíduos, 106 pacientes e 135 controles saudáveis. A genotipagem foi realizada utilizando PCR em tempo real. A variante rs3857059 se mostrou associada a PD em mexicano-mestiços (OR = 2,40, IC 1,1-5,1, p = 0,02) sob o modelo recessivo. Além disso, um efeito de gênero foi encontrado para o genótipo GG no sexo feminino (OR = 1,31, CI, 1,01-1,7, p = 0,037). Este é o primeiro estudo que confirma associação da variante rs3857059 para a PD e também um efeito de gênero. Nossos dados contribuem para elucidar suscetibilidade à PD observada na população mexicana-mestiça.

Genetic structure and forensic parameters of 38 Indels for human identification purposes in eight Mexican populations.

Insertion-deletions for human identification purposes (HID-Indels) offer advantages to solve particular forensic situations and complex paternity cases. In Mexico, admixed population known as Mestizos is the largest (∼90%), plus a number of Amerindian groups (∼10%), which have not been studied with HID-Indels. For this reason, allele frequencies and forensic parameters for 38 HID-Indels were estimated in 531 unrelated individuals from one Amerindian (Purépecha) and seven Mestizo populations from different regions of the country. Genotype distribution was in agreement with Hardy-Weinberg expectations in almost all loci/populations. The linkage disequilibrium (LD) test did not reveal possible associations between loci pairs in all eight Mexican populations. The combined power of discrimination was high in all populations (PD >99.99999999998%). However, the power of exclusion of the 38 HID-Indel system (PE >99.6863%) was reduced regarding most of autosomal STR kits. The assessment of genetic structure (AMOVA) and relationships between populations (FST) demonstrated significant differences among Mexican populations, mainly of the Purépecha Amerindian group. Among Mexican-Mestizos, three population clusters consistent with geography were defined: (i) North-West region: Chihuahua, Sinaloa, and Jalisco; (ii) Central-Southern region: Mexico City, Veracruz and Yucatan; (iii) South region: Chiapas. In brief, this report validates the inclusion of the 38 HID-Indel system in forensic casework and paternity cases in seven Mexican-Mestizo populations from different regions, and in one Mexican Amerindian group.

Association of the rs1801133 variant in the MTHFR gene and sporadic Parkinson's disease.

The MTHFR gene has been reported as a susceptibility locus for sporadic Parkinson's disease (sPD). The functional variant rs1801133 has been linked to hyperhomocysteinemia and dopaminergic cell death. Among different populations, Mexican-Mestizos (most present-day Mexicans) have the highest frequency of this variant. Therefore, we sought to determine a possible association of rs1801133 with SPD. In total, 356 individuals were included: 140 patients with PD, diagnosed according to the Queen Square Brain Bank criteria, and 216 neurologically healthy controls. Genotyping was performed using TaqMan probes for rs1801133 and real-time PCR. Logistic regression analysis with adjustment for smoking and gender was used to test for an association between genotype and SPD. The CC genotype was associated with SPD; exp() = 2.06; 95% CI: 1.101-3.873, p = 0.024. No association with age at onset, cognitive impairment or gender was found in our study group. Our data suggest an important role of MTHFR gene variants in SPD.

Duchenne muscular dystrophy in a developing country: challenges in management and genetic counseling.

BACKGROUND AND OBJECTIVE: Multidisciplinary management of Duchenne Muscular Dystrophy (DMD) has achieved outstanding results in developed nations. We aimed to describe the status of diagnosis and management of DMD in a developing country through the experience of non-profit organizations. METHODS: A Multistate, multiple-source, population-based survey was performed from medical records of 432 patients. Data were retrospectively collected, reviewed and curated by health specialists; including clinical features, age at first symptoms, age at diagnosis, disease progression and management, family history, education, age and cause of death. RESULTS: There is a delay in noticing first symptoms and it did not diminish over the past 20 years. Less than 30% of patients obtained definite diagnosis and most of them are in physiotherapy programs but not under steroid treatment. In our study, family history does not anticipate recognition of symptoms compared to sporadic cases (p = 0.05). Approximately 93.33% of our patients attended to education programs. Mean age at death was 18.94 +/- 6.73 years and the most frequent cause was pneumonia. CONCLUSION: Delayed diagnosis of DMD in Mexico is mainly caused by the late detection of first symptoms. There is no difference in early detection of symptoms between familiar and sporadic cases. Lifespan of patients in our cohort is reduced compared to developed countries. The late diagnosis and low percentage of definite cases may affect patient management and genetic counseling and could also preclude participation of patients into novel clinical trials.

A new de novo mutation in a non-hot spot region at the DMD gene in a Mexican family.

In this report we present the analysis of a sporadic case of DMD and his family. In the present case, a deletion of exons 18-47 is presented which predicts abolition of the reading frame and is located between the well-known deletion hot spots of the DMD gene. This mutation was not previously reported in the Leiden database (LOVD). Both MLPA and segregation analysis with short tandem repeat markers elucidated the status of the mother, sister and the younger brother of the proband, who were not carriers of the mutation. This case provides a description of a new pathogenic variant presented as de novo mutation in a DMD patient. Haplotype analysis and complete gene screening may improve genetic counseling in cases of germline mosaicism and de novo mutations.

[Duchenne muscular dystrophy: current aspects and perspectives on treatment]. / Distrofia muscular de Duchenne: actualidad y perspectivas de tratamiento.

INTRODUCTION AND DEVELOPMENT: Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease of genetic origin that affects male children. It is characterized by progressive muscle deterioration which results in the patient becoming wheelchair-dependent until death from cardio-respiratory complications. A few years ago, DMD patients' life quality and expectancy were poor and treatment options limited; valuable recommendations that significantly delay the progress of the disease and improve the patient's life quality have been brought about recently. Numerous therapeutic approaches are now in development in order to correct the DMD genetic defect at molecular level. In the mean time, a comprehensive system to maintain patients in their best possible physical condition is needed. CONCLUSIONS: Accurate detection of complications enables caregivers to determine which patients are at higher risk and to provide treatment accordingly. Nevertheless, all of these efforts are dependent on early clinical and molecular diagnosis, careful record of clinical changes and long-term follow-up of DMD patients. Furthermore, the involvement of multidisciplinary groups and the patient's family is essential in said interventions.