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Improving the diagnosis of cobalamin and related defects by genomic analysis, plus functional and structural assessment of novel variants

Overview of attention for article published in Orphanet Journal of Rare Diseases, July 2018
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (51st percentile)

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4 tweeters
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2 Facebook pages

Citations

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1 Dimensions

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13 Mendeley
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Title
Improving the diagnosis of cobalamin and related defects by genomic analysis, plus functional and structural assessment of novel variants
Published in
Orphanet Journal of Rare Diseases, July 2018
DOI 10.1186/s13023-018-0862-y
Pubmed ID
Authors

Sandra Brasil, Fátima Leal, Ana Vega, Rosa Navarrete, María Jesús Ecay, Lourdes R. Desviat, Casandra Riera, Natàlia Padilla, Xavier de la Cruz, Mari Luz Couce, Elena Martin-Hernández, Ana Morais, Consuelo Pedrón, Luis Peña-Quintana, Miriam Rigoldi, Norma Specola, Isabel Tavares de Almeida, Inmaculada Vives, Raquel Yahyaoui, Pilar Rodríguez-Pombo, Magdalena Ugarte, Celia Pérez-Cerda, Begoña Merinero, Belén Pérez

Abstract

Cellular cobalamin defects are a locus and allelic heterogeneous disorder. The gold standard for coming to genetic diagnoses of cobalamin defects has for some time been gene-by-gene Sanger sequencing of individual DNA fragments. Enzymatic and cellular methods are employed before such sequencing to help in the selection of the gene defects to be sought, but this is time-consuming and laborious. Furthermore some cases remain undiagnosed because no biochemical methods have been available to test for cobalamin absorption and transport defects. This paper reports the use of massive parallel sequencing of DNA (exome analysis) for the accurate and rapid genetic diagnosis of cobalamin-related defects in a cohort of affected patients. The method was first validated in an initial cohort with different cobalamin defects. Mendelian segregation, the frequency of mutations, and the comprehensive structural and functional analysis of gene variants, identified disease-causing mutations in 12 genes involved in the absorption and synthesis of active cofactors of vitamin B12 (22 cases), and in the non-cobalamin metabolism-related genes ACSF3 (in four biochemically misdiagnosed patients) and SUCLA2 (in one patient with an unusual presentation). We have identified thirteen new variants all classified as pathogenic according to the ACGM recommendation but four were classified as variant likely pathogenic in MUT and SUCLA2. Functional and structural analysis provided evidences to classify them as pathogenic variants. The present findings suggest that the technology used is sufficiently sensitive and specific, and the results it provides sufficiently reproducible, to recommend its use as a second-tier test after the biochemical detection of cobalamin disorder markers in the first days of life. However, for accurate diagnoses to be made, biochemical and functional tests that allow comprehensive clinical phenotyping are also needed.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 13 100%

Demographic breakdown

Readers by professional status Count As %
Librarian 2 15%
Other 2 15%
Student > Doctoral Student 2 15%
Student > Master 2 15%
Student > Bachelor 1 8%
Other 2 15%
Unknown 2 15%
Readers by discipline Count As %
Medicine and Dentistry 5 38%
Biochemistry, Genetics and Molecular Biology 5 38%
Pharmacology, Toxicology and Pharmaceutical Science 1 8%
Arts and Humanities 1 8%
Unknown 1 8%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 March 2019.
All research outputs
#9,154,937
of 16,534,657 outputs
Outputs from Orphanet Journal of Rare Diseases
#935
of 1,759 outputs
Outputs of similar age
#132,423
of 281,664 outputs
Outputs of similar age from Orphanet Journal of Rare Diseases
#3
of 3 outputs
Altmetric has tracked 16,534,657 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,759 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.4. This one is in the 43rd percentile – i.e., 43% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 281,664 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.
We're also able to compare this research output to 3 others from the same source and published within six weeks on either side of this one.