Genetics and genomic medicine in Argentina

Vishnopolska, Sebastián Alexis; Turjanski, Adrián; Piñero, Mariana Herrera; Groisman, Boris; Liascovich, Rosa; Chiesa, Ana; Martí, Marcelo A.

doi:10.1002/mgg3.455

Cited by 23 publications

(23 citation statements)

References 22 publications

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“…The genetic tests performed in these centers include cytogenetics, Fluorescence in situ hybridization (FISH), and NGS (Centro Nacional de Genética Médica, 2017b). There are around 20 NGS devices in the country and sequencing is performed both locally and outsourced to other countries such as Brazil and Spain (Vishnopolska, 2018). Array‐CGH was introduced by CENAGEM in 2014 and is currently being incorporated by other institutions as well (Cotignola, 2019).…”

Section: Introductionmentioning

confidence: 99%

Ophthalmic genetics in South America

Varela

Moya

Schlottmann³

et al. 2020

American J of Med Genetics Pt C

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South America comprises of heterogeneous topographies, populations, and health care systems. Therefore, it is not surprising to see differences among the countries regarding expertise, education, and practices of ophthalmic genetics for patients with rare eye diseases. Nevertheless, common challenges such as limited genetics training in medical schools and among ophthalmologists, scarcity of diagnostic tools for phenotyping, and expensive genetic testing not covered by the public healthcare systems, are seen in all of them. Here, we provide a detailed report of the current status of ophthalmic genetics, described by the personal views of local ophthalmologists from Brazil, Colombia, Argentina, and Chile. By reporting our strengths and weaknesses as a region, we intend to highlight the need for guidelines on how to manage these patients aligned with public health policies. Our region contributes to research worldwide, with thousands of well diagnosed patients from a number of unique and genetically diverse populations. The constant expansion of ophthalmic genetics and molecular diagnostics requires us to join forces to collaborate across South America and with other countries to improve access to next-generation diagnostics and ultimately improve patient care.

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Section: Introductionmentioning

confidence: 99%

Ophthalmic genetics in South America

Varela

Moya

Schlottmann³

et al. 2020

American J of Med Genetics Pt C

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“…Since then, among the settled programs, the ones of Buenos Aires Province, and FEI (Fundación de Endocrinología Infantil) (a non-profit private institution ) found in >6.000.000 births and incidence of PKU and HPA of 1:13000. [12] The detected patients are followed in two specialized centers.…”

Section: Introductionmentioning

confidence: 99%

Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients

Enacan

Miñana

Fernández

et al. 2019

J. inborn errors metab. screen.

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Phenylketonuria (PKU, OMIM 261600) is predominantly caused by mutations in the PAH gene. One hundred and three Argentine PKU patients were studied by Sanger sequencing; 101 were completely characterized (90.3% were compound heterozygotes). Fifty-four different pathogenic variants were identified. Mutations were distributed all along the PAH gene but concentrated in exon 7 (26%), 12 (12%), 11 (10%), and 6 (10%). 77% were missense, and 77% affected the enzyme catalytic domain, nine mutations accounted for 57% of 179 studied alleles: p.

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“…Combined with conventional Sanger sequencing in another family, this revealed four missense variants in exon 2 of the POU1F1 beta isoform, each in an unrelated family ( Figure 1A, 2A ). The four patient POU1F1 missense variants are absent from gnomAD and in-house population-matched exome databases 39,40 , and they are predicted to be damaging by several bioinformatic algorithms ( Table 1 ). Remarkably, these variants clustered in four consecutive codons: c.148T>G (p.S50A), c.152T>G (p.I51S), c.155T>G (p.L52W), and c.157T>G (p.S53A) in NM 001122757.3 ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

High-throughput splicing assays identify missense and silent splice-disruptivePOU1F1variants underlying pituitary hormone deficiency

Gergics

Smith

Bando

et al. 2021

Preprint

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Pituitary hormone deficiency occurs in ~1:4,000 live births. Approximately 3% of the cases are due to mutations in the alpha isoform of POU1F1, a pituitary-specific transcriptional activator. We found four separate heterozygous missense variants in unrelated hypopituitarism patients that were predicted to affect a minor isoform, POU1F1 beta, which can act as a transcriptional repressor. These variants retain repressor activity, but they shift splicing to favor the expression of the beta isoform, resulting in dominant negative loss of function. Using a high throughput splicing reporter assay, we tested 1,080 single nucleotide variants in POU1F1. We identified 113 splice disruptive variants, including 23 synonymous variants. We evaluated separate cohorts of hypopituitarism patients and found two different synonymous splice disruptive variants that co-segregate with hypopituitarism. This study underlines the importance of evaluating the impact of variants on splicing and provides a catalog for interpretation of variants of unknown significance in the POU1F1 gene.

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Genetics and genomic medicine in Argentina

Abstract: A historical summary of genetics and genomic medicine in Argentina. We go through the achievements and difficulties in the implementation of genetic and genomic services both in academia and health care.

Cited by 23 publications

References 22 publications

Ophthalmic genetics in South America

Ophthalmic genetics in South America

Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients

High-throughput splicing assays identify missense and silent splice-disruptivePOU1F1variants underlying pituitary hormone deficiency

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