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Analysis of institutional authors

Ugarte MAuthorRodriguez-Pombo PAuthorPerez BCorresponding Author

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December 26, 2022
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Article

Pathogenic variants of the coenzyme A biosynthesis-associated enzyme phosphopantothenoylcysteine decarboxylase (PPCDC) cause autosomal-recessive dilated cardiomyopathy

Publicated to: Journal Of Inherited Metabolic Disease. 46 (2): 261-272 - 2023-03-01 46(2), DOI: 10.1002/jimd.12584

Authors:

Bravo-Alonso, I; Morin, M; Arribas-Carreira, L; Alvarez, M; Pedrón-Giner, C; Soletto, L; Santolaria, C; Ramón-Maiques, S; Ugarte, M; Rodríguez-Pombo, P; Ariño, J; Moreno-Pelayo, MA; Pérez, B
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Affiliations

Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular, Universidad Autónoma de Madrid, CIBERER, IdiPAZ, Madrid, Spain. - Author
CIBERER-ISCIII), Madrid, Spain. - Author
Hosp Infantil Univ Nino Jesus, Secc Gastroenterol & Nutr, Madrid, Spain - Author
Hosp Univ Ramon y Cajal, Serv Genet, IRYCIS, Madrid, Spain - Author
Inst Biomed Valencia IBV CSIC CIBERER, Valencia, Spain - Author
Inst Salud Carlos III CB06 07 0048 CIBERER ISCIII, Ctr Invest Biomed Red Enfermedades Raras, Madrid, Spain - Author
Institut de Biotecnologia i Biomedicina & Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain. - Author
Instituto de Biomedicina de Valencia (IBV) CSIC, Valencia, Spain. - Author
Sección de Gastroenterología y Nutrición, Hospital Infantil Universitario Niño Jesús, Av. de Menéndez Pelayo 65, Madrid, Spain. - Author
Servicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS, Carretera de Colmenar km 9.100, 28034 Madrid, Spain. Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III (CB06/07/0048 - Author
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Cerdanyola Del Valles, Spain - Author
Univ Autonoma Madrid, Ctr Diagnost Enfermedades Mol, Ctr Biol Mol, IdiPAZ, Madrid 28049, Spain - Author
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Abstract

Coenzyme A (CoA) is an essential cofactor involved in a range of metabolic pathways including the activation of long-chain fatty acids for catabolism. Cells synthesize CoA de novo from vitamin B5 (pantothenate) via a pathway strongly conserved across prokaryotes and eukaryotes. In humans, it involves five enzymatic steps catalyzed by four enzymes: pantothenate kinase (PANK [isoforms 1-4]), 4'-phosphopantothenoylcysteine synthetase (PPCS), phosphopantothenoylcysteine decarboxylase (PPCDC), and CoA synthase (COASY). To date, inborn errors of metabolism associated with all of these genes, except PPCDC, have been described, two related to neurodegeneration with brain iron accumulation (NBIA), and one associated with a cardiac phenotype. This paper reports another defect in this pathway (detected in two sisters), associated with a fatal cardiac phenotype, caused by biallelic variants (p.Thr53Pro and p.Ala95Val) of PPCDC. PPCDC enzyme (EC 4.1.1.36) catalyzes the decarboxylation of 4'-phosphopantothenoylcysteine to 4'-phosphopantetheine in CoA biosynthesis. The variants p.Thr53Pro and p.Ala95Val affect residues highly conserved across different species; p.Thr53Pro is involved in the binding of flavin mononucleotide, and p.Ala95Val is likely a destabilizing mutation. Patient-derived fibroblasts showed an absence of PPCDC protein, and nearly 50% reductions in CoA levels. The cells showed clear energy deficiency problems, with defects in mitochondrial respiration, , and mostly glycolytic ATP synthesis. Functional studies performed in yeast suggest these mutations to be functionally relevant. In summary, this work describes a new, ultra-rare, severe inborn error of metabolism due to pathogenic variants of PPCDC.This article is protected by copyright. All rights reserved.
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Keywords

coadilated cardiomyopathygenehal3inborn errors of metabolisminhibitory subunitmutationspank2ppcdcsaccharomyces-cerevisiaesit4yeastBiosynthesis of coenzyme aCarboxy-lyasesCardiomyopathy, dilatedCoenzyme aDilated cardiomyopathyFunctional-characterizationHeartHumansInborn errors of metabolismPhosphopantothenoyl-cysteine decarboxylasePpcdcSaccharomyces cerevisiae

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal of Inherited Metabolic Disease due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2023, it was in position 37/191, thus managing to position itself as a Q1 (Primer Cuartil), in the category Genetics & Heredity.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 2.81. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 13, 2025)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.29 (source consulted: FECYT Mar 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2026-04-05, the following number of citations:

  • WoS: 15
  • Scopus: 8
  • Europe PMC: 4
  • Google Scholar: 9
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-05:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 20.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 20 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 8.
  • The number of mentions on the social network X (formerly Twitter): 11 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://repositorio.uam.es/handle/10486/705989
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Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Bravo-Alonso I) and Last Author (PEREZ GONZALEZ, MARIA BELEN).

the author responsible for correspondence tasks has been PEREZ GONZALEZ, MARIA BELEN.

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Awards linked to the item

This work was funded by the Instituto de Salud Carlos (ISCIII), the European Regional Development Fund [PI19/01155], the Ministerio de Economia, Industria y Competitividad, Spain (BFU2017-82574-P), and the Consejeria de Educacion, Juventud y Deporte, Comunidad de Madrid [B2017/BMD3721].
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