Genetics and Genomic Medicine in Colombia

Castro, Mauricio De; Restrepo, Carlos Martín

doi:10.1002/mgg3.139

Cited by 24 publications

(22 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This would be particularly useful in families for whom genetic, biochemical, or imaging studies are too costly or scantily available, which is often the case in communities characterized by a high prevalence of neurodegenerative disorders. For example, the region targeted in our study (Juan de Acosta, Colombia) is a genetic isolate including high rates of poverty alongside high rates of familial HD (Castilhos et al ., ; De Castro & Restrepo, ). In contexts such as this, the proposed extensions of the present study could promote useful breakthroughs in the quest for sensitive, affordable, and widely available biomarkers of prodromal frontostriatal atrophy.…”

Section: Discussionmentioning

confidence: 99%

Action‐semantic and syntactic deficits in subjects at risk for Huntington's disease

García

Bocanegra

Herrera

et al. 2017

Journal of Neuropsychology

View full text Add to dashboard Cite

Frontostriatal networks play critical roles in grounding action semantics and syntactic skills. Indeed, their atrophy distinctively disrupts both domains, as observed in patients with Huntington's disease (HD) and Parkinson's disease, even during early disease stages. However, frontostriatal degeneration in these conditions may begin up to 15 years before the onset of clinical symptoms, opening avenues for pre-clinical detection via sensitive tasks. Such a mission is particularly critical in HD, given that patients' children have 50% chances of inheriting the disease. Against this background, we assessed whether deficits in the above-mentioned domains emerge in subjects at risk to develop HD. We administered tasks tapping action semantics, object semantics, and two forms of syntactic processing to 18 patients with HD, 19 asymptomatic first-degree relatives, and sociodemographically matched controls for each group. The patients evinced significant deficits in all tasks, but only those in the two target domains were independent of overall cognitive state. More crucially, relative to controls, the asymptomatic relatives were selectively impaired in action semantics and in the more complex syntactic task, with both patterns emerging irrespective of the subjects' overall cognitive state. Our findings highlight the relevance of these dysfunctions as potential prodromal biomarkers of HD. Moreover, they offer theoretical insights into the differential contributions of frontostriatal hubs to both domains while paving the way for innovations in diagnostic procedures.

show abstract

Section: Discussionmentioning

confidence: 99%

Action‐semantic and syntactic deficits in subjects at risk for Huntington's disease

García

Bocanegra

Herrera

et al. 2017

Journal of Neuropsychology

View full text Add to dashboard Cite

show abstract

“…Although the indication for referring a patient for an aCGH test has previously been defined in the literature [ 13 ], in the light of recent methodological advances and redefinition of the pathognomonic significance of the chromosomal anomalies eventually detected, it is necessary to periodically review the diagnostic yield of this molecular technique [ 11 ]. Such periodic review is particularly important in developing countries where the infrastructure of genetic laboratories is, in many cases, still relatively rudimentary [ 14 ], and also where healthcare insurance imposes access barriers for patients [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

CGH analysis in Colombian patients: findings of 1374 arrays in a seven-year study

2018

View full text Add to dashboard Cite

BackgroundArray-based comparative genome hybridization (array CGH) is a first-line test used in the genetic evaluation of individuals with multiple anomalies, developmental delays, and cognitive deficits. In this study, we analyzed clinical indications and findings of array CGH tests of Colombian individuals forwarded to a reference laboratory over a period of seven years in order to evaluate the diagnostic performance of the test in our population.ResultsThe results of 1374 array CGH analyses of Colombian individuals were referred to the Andean Reference Institute in Colombia (Instituto de Referencia Andino) during a 7-year period (2009–2015). Chromosomal imbalances were detected in 488 cases (35%), whereas 121 cases were classified as nonpathogenic variants, 65 cases (4.7%) were classified as variants of uncertain significance, and 302 cases (22%) were classified as abnormal or pathogenic. The most common findings in the abnormal and/or pathogenic set were deletions, followed by duplications and complex rearrangements. Variants in the carrier status of autosomal recessive diseases were identified as incidental findings in 29 subjects (2%).ConclusionsClinical indications preceding the referral of aCGH in Colombian patients are not standardized and result in unexpected pathogenic variants as well as secondary findings that need careful interpretation. Development of local infrastructure will probably improve the communication between all stakeholders, to ensure accurate clinical diagnoses.

show abstract

“… 21 Colombia has ~50 million inhabitants; 49% of the population is mestizo (European and Amerindian ancestries), 37% has European origin, 10% has African ancestry, and 3.4% is Amerindian. 22 …”

Section: Introductionmentioning

confidence: 99%

Creating and validating a warfarin pharmacogenetic dosing algorithm for Colombian patients

Gálvez¹,

Restrepo²,

Contreras³

et al. 2018

PGPM

View full text Add to dashboard Cite

PurposeWarfarin is an oral anticoagulant associated with adverse reaction to drugs due to wide inter- and intra-individual dosage variability. Warfarin dosage has been related to non-genetic and genetic factors. CYP2C9 and VKORC1 gene polymorphisms affect warfarin metabolism and dosage. Due to the central role of populations’ ethnical and genetic origin on warfarin dosage variability, novel algorithms for Latin American subgroups are necessary to establish safe anticoagulation therapy.Patients and methodsWe genotyped CYP2C9*2 (c.430C > T), CYP2C9*3 (c.1075A > C), CYP4F2 (c.1297G > A), and VKORC1 (−1639 G > A) polymorphisms in 152 Colombian patients who received warfarin. We evaluated the impact on the variability of patients’ warfarin dose requirements. Multiple linear regression analysis, using genetic and non-genetic variables, was used for creating an algorithm for optimal warfarin maintenance dose.ResultsMedian weekly prescribed warfarin dosage was significantly lower in patients having the VKORC1-1639 AA genotype and poor CYP2C9*2/*2,*2/*3 metabolizers than their wild-type counterparts. We found a 2.3-fold increase in mean dose for normal sensitivity patients (wild-type VKORC1/CYP2C9 genotypes) compared to the other groups (moderate and high sensitivity); 31.5% of the patients in our study group had warfarin sensitivity-related genotypes. The estimated regression equation accounted for 44.4% of overall variability in regard to warfarin maintenance dose. The algorithm was validated, giving 45.9% correlation (R2=0.459).ConclusionOur results describe and validate the first algorithm for predicting warfarin maintenance in a Colombian mestizo population and have contributed toward the understanding of pharmacogenetics in a Latin American population subgroup.

show abstract

Genetics and Genomic Medicine in Colombia

Abstract: Genetics and Genomic medicine in Colombia.

Cited by 24 publications

References 24 publications

Action‐semantic and syntactic deficits in subjects at risk for Huntington's disease

Action‐semantic and syntactic deficits in subjects at risk for Huntington's disease

CGH analysis in Colombian patients: findings of 1374 arrays in a seven-year study

Creating and validating a warfarin pharmacogenetic dosing algorithm for Colombian patients

Contact Info

Product

Resources

About