Publications by authors named "Rosario Paredes"

6 Publications

  • Page 1 of 1

Multi-institutional experience of genetic diagnosis in Ecuador: National registry of chromosome alterations and polymorphisms.

Mol Genet Genomic Med 2020 02 12;8(2):e1087. Epub 2019 Dec 12.

Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador.

Background: Detection of chromosomal abnormalities is crucial in various medical areas; to diagnose birth defects, genetic disorders, and infertility, among other complex phenotypes, in individuals across a wide range of ages. Hence, the present study wants to contribute to the knowledge of type and frequency of chromosomal alterations and polymorphisms in Ecuador.

Methods: Cytogenetic registers from different Ecuadorian provinces have been merged and analyzed to construct an open-access national registry of chromosome alterations and polymorphisms.

Results: Of 28,806 karyotypes analyzed, 6,008 (20.9%) exhibited alterations. Down syndrome was the most frequent autosome alteration (88.28%), followed by Turner syndrome (60.50%), a gonosome aneuploidy. A recurrent high percentage of Down syndrome mosaicism (7.45%) reported here, as well as by previous Ecuadorian preliminary registries, could be associated with geographic location and admixed ancestral composition. Translocations (2.46%) and polymorphisms (7.84%) were not as numerous as autosomopathies (64.33%) and gonosomopathies (25.37%). Complementary to conventional cytogenetics tests, molecular tools have allowed identification of submicroscopic alterations regions or candidate genes which can be possibly implicated in patients' symptoms and phenotypes.

Conclusion: The Ecuadorian National Registry of Chromosome Alterations and Polymorphisms provides a baseline to better understand chromosomal abnormalities in Ecuador and therefore their clinical management and awareness. This data will guide public policy makers to promote and financially support cytogenetic and genetic testing.
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February 2020

Localisation of weakly interacting bosons in two dimensions: disorder vs lattice geometry effects.

Sci Rep 2019 Jul 30;9(1):11049. Epub 2019 Jul 30.

Instituto de Física, Universidad Nacional Autónoma de México, Apartado Postal 20-364, México, D. F. 01000, Mexico.

We investigate the effects of disorder and lattice geometry against localisation phenomena in a weakly interacting ultracold bosonic gas confined in a 2D optical lattice. The behaviour of the quantum fluid is studied at the mean-field level performing computational experiments, as a function of disorder strength for lattices of sizes similar to current experiments. Quantification of localisation, away from the Bose glass phase, was obtained directly from the stationary density profiles through a robust statistical analysis of the condensate component, as a function of the disorder amplitude. Our results show a smooth transition, or crossover, to localisation induced by disorder in square and triangular lattices. In contrast, associated to its larger tunneling amplitude, honeycomb lattices show absence of localisation for the same range of disorder strengths and same lattice amplitude, while also exhibiting partial localisation for large disorder amplitudes. We also conclude that the coordination number z have a partial influence on how fast this smooth transition occurs as the system size increases. Signatures of disorder are also found in the ground state energy spectrum, where a continuous distribution emerges instead of a distribution of sharp peaks proper to the system in the absence of disorder.
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July 2019

Association between the APOE 4 Allele and Late-Onset Alzheimer's Disease in an Ecuadorian Mestizo Population.

Int J Alzheimers Dis 2017 4;2017:1059678. Epub 2017 Dec 4.

Hospital de Especialidades FFAA, Quito, Pichincha, Ecuador.

Alzheimer's disease (AD) is the most common neurodegenerative disease. It has two main pathological hallmarks: amyloid plaques and neurofibrillary tangles. The APOE 4 allele has been recognized as the strongest genetic risk factor for late-onset Alzheimer's disease (LOAD) in several populations worldwide, yet the risk varies by region and ethnicity. The aims of this study were to describe APOE allele and genotype frequencies and examine the relationship between the APOE 4 allele and LOAD risk in an Ecuadorian Mestizo population. We carried out a case-control study comprising 56 individuals clinically diagnosed with probable AD (≥65 years of age) and 58 unrelated healthy control subjects (≥65 years of age). Genotyping was performed using the real-time PCR method. Our data showed that allelic and genotypic frequencies follow the trends observed in most worldwide populations. We also found a high-risk association between APOE 4 allele carriers and LOAD (OR = 7.286; 95% CI = 2.824-18.799; < 0.001). Therefore, we concluded that APOE 4 must be considered an important genetic risk factor for LOAD in the Ecuadorian Mestizo population. Additionally, we suggest that in mixed populations the effects of admixture and ethnic identity should be differentiated when evaluating genetic contributions to Alzheimer's disease risk.
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December 2017

Novel EYA1 variants causing Branchio-oto-renal syndrome.

Int J Pediatr Otorhinolaryngol 2017 Jul 26;98:59-63. Epub 2017 Apr 26.

John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA. Electronic address:

Introduction: Branchio-oto-renal (BOR) syndrome is an autosomal dominant genetic disorder characterized by second branchial arch anomalies, hearing impairment, and renal malformations. Pathogenic mutations have been discovered in several genes such as EYA1, SIX5, and SIX1. However, nearly half of those affected reveal no pathogenic variant by traditional genetic testing.

Methods And Materials: Whole Exome sequencing and/or Sanger sequencing performed in 10 unrelated families from Turkey, Iran, Ecuador, and USA with BOR syndrome in this study.

Results: We identified causative DNA variants in six families including novel c.525delT, c.979T > C, and c.1768delG and a previously reported c.1779A > T variants in EYA1. Two large heterozygous deletions involving EYA1 were detected in additional two families. Whole exome sequencing did not reveal a causative variant in the remaining four families.

Conclusions: A variety of DNA changes including large deletions underlie BOR syndrome in different populations, which can be detected with comprehensive genetic testing.
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July 2017

Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort.

Genet Med 2016 Apr 30;18(4):364-71. Epub 2015 Jul 30.

Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.

Purpose: Autosomal recessive nonsyndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity, with reported mutations in 58 different genes. This study was designed to detect deafness-causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES).

Methods: After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador, and Puerto Rico to screen for mutations in all known ARNSD genes.

Results: We detected ARNSD-causing variants in 90 (56%) families, 54% of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13%), MYO7A (11%), SLC26A4 (10%), TMPRSS3 (9%), TMC1 (8%), ILDR1 (6%), and CDH23 (4%). Nine mutations were detected in multiple families with shared haplotypes, suggesting founder effects.

Conclusion: We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56% of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.Genet Med 18 4, 364-371.
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April 2016

Novel domain-specific POU3F4 mutations are associated with X-linked deafness: examples from different populations.

BMC Med Genet 2015 Feb 25;16. Epub 2015 Feb 25.

John P. Hussmann Institute for Human Genomics and John T. Macdonald Foundation, Department of Human Genetics, Miller school of Medicine, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA.

Background: Mutations in the POU3F4 gene cause X-linked deafness type 3 (DFN3), which is characterized by inner ear anomalies.

Methods: Three Turkish, one Ecuadorian, and one Nigerian families were included based on either inner ear anomalies detected in probands or X-linked family histories. Exome sequencing and/or Sanger sequencing were performed in order to identify the causative DNA variants in these families.

Results: Four novel, c.707A>C (p.(Glu236Ala)), c.772delG (p.(Glu258ArgfsX30)), c.902C>T (p.(Pro301Leu)), c.987T>C (p.(Ile308Thr)), and one previously reported mutation c.346delG (p.(Ala116ProfsX26)) in POU3F4, were identified. All mutations identified are predicted to affect the POU-specific or POU homeo domains of the protein and co-segregated with deafness in all families.

Conclusions: Expanding the spectrum of POU3F4 mutations in different populations along with their associated phenotypes provides better understanding of their clinical importance and will be helpful in clinical evaluation and counseling of the affected individuals.
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February 2015