Discovery of novel genetic syndromes in Latin America: Opportunities and challenges

Faundes, Víctor; Repetto, Gabriela M.; Valdivia, Leonardo E.

doi:10.1590/1678-4685-GMB-2023-0318

Víctor Faundes

conceived

defined

wrote the manuscript

design the figures

read and approved the final version

Universidad de Chile, Instituto de Nutrición y Tecnología de los Alimentos, Laboratorio de Genética y Enfermedades Metabólicas, Santiago, Chile.

https://orcid.org/0000-0002-6746-0103

Gabriela M. Repetto

added substantial viewpoints and comments in terms of clinical and model organisms research

read and approved the final version

Universidad del Desarrollo, Facultad de Medicina, Instituto de Ciencias e Innovación en Medicina, Centro de Genética y Genómica, Programa de Enfermedades Raras, Santiago, Chile.

Leonardo E. Valdivia

added substantial viewpoints and comments in terms of clinical and model organisms research

read and approved the final version

Universidad Mayor, Facultad de Ciencias, Centro de Biología Integrativa, Santiago, Chile.

Universidad Mayor, Facultad de Ciencias, Escuela de Biotecnología, Santiago, Chile.

Send correspondence to
Víctor Faundes. Universidad de Chile, Instituto de Nutrición y Tecnología de los Alimentos, Laboratorio de Genética y Enfermedades Metabólicas, Avenida El Líbano, 5524, 7830490, Santiago, Chile. E-mail: vfaundes@inta.uchile.cl

Associate Editor:

Carlos F. M. Menck

Conflict of Interest

The authors declare no conflict of interest.

Figures (3)
Tables (1)

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Figure 1 -
Correlation between estimated population of Latin American countries and their mentions in OMIM entries. The population estimations were obtained from wikipedia.orgWikipedia, Wikipedia, https://www.wikipedia.org/ (accessed 9 June 2023)
https://www.wikipedia.org/... , which in turn obtained those numbers from international or national official organisations, whereas the OMIM entries were searched using the terms “country name” OR “its demonym” (e.g. Argentina OR Argentinian). The results were retrieved from both sources on 9th June 2023.

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Figure 2 -
Steps currently performed for the discovery of novel gene-disease associations. The workflow of discovery of novel genetic syndromes is summarised in 9 basic and critical steps, from the evaluation of an index patient to the confirmation of the novel condition over time, considering how this type of research is performed nowadays with current techniques. 1) Clinical evaluation and requisition of genomic test, 2) return of negative results in already-associated genes, 3) analysis of raw data focused on unreported genes/variants, 4) identification of candidate variant(s)/gene according to metrics, 5) checking of previous findings using ClinGen criteria, 6) submission of clinical and genetic data to repositories, 7) comparison of clinical data amongst patients and development of functional studies, 8) publication of NGDA, and 9) expansion of evidence with further cohorts and functional data. Created with BioRender.com.

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Figure 3 -
Opportunities and challenges that LatAm has to contribute to the discovery of NGDA. The opportunities (denoted with a green tick) and challenges (denoted with a red cross) of the continent are summarised in the same steps described for the discovery of NGDA workflow. Abbreviations and symbols: BI=Bioinformatics/Bioinformatician, #=Number, ↑=Increase. Created with BioRender.com.

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Table 1 -
Past and current contributions of Latin American geneticists to the discovery of novel genetic syndromes.

Syndrome (OMIM #)	Geneticist (Country of Origin)	Year of Publication	Studied Population	References
Mucopolysaccharidosis Type IVa (253000)	Luis Morquio (Uruguay)	1929	Uruguayan	(Baujat and Valayannopoulos, 2014Baujat G and Valayannopoulos V (2014) [Natural history of morquio a disease]. Arch Pediatr 21:S32-38.)
Cantu syndrome (239850)	José María Cantú (Mexico)	1982	Mexican	(Cantu et al., 1982Cantu JM, Garcia-Cruz D, Sanchez-Corona J, Hernandez A and Nazara Z (1982) A distinct osteochondrodysplasia with hypertrichosis- individualization of a probable autosomal recessive entity. Hum Genet 60:36-41.)
Huntington’s disease (143100)	Ernesto Bonilla (Venezuela)	1983 and 1993	Venezuelan	(Gusella et al., 1983Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi RE, Watkins PC, Ottina K, Wallace MR, Sakaguchi AY et al. (1983) A polymorphic DNA marker genetically linked to Huntington’s disease. Nature 306:234-238.; The Huntington’s Disease Collaborative Research Group, 1993The Huntington’s Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72:971-983.)
Richieri-Costa/Guion-Almeida syndrome (268850)	Antonio Richieri-Costa and María Leine Guión-Almeida (Brazil)	1992	Brazilian	(Richieri-Costa and Guion-Almeida, 1992Richieri-Costa A and Guion-Almeida ML (1992) Short stature, mental retardation, eye anomalies, and cleft lip/palate. Am J Med Genet 42:449-452.)
Steel syndrome (615155)	Claudia Gonzaga-Jauregui (Mexico)	2015	Puerto Rican	(Gonzaga-Jauregui et al., 2015Gonzaga-Jauregui C, Gamble CN, Yuan B, Penney S, Jhangiani S, Muzny DM, Gibbs RA, Lupski JR and Hecht JT (2015) Mutations in col27a1 cause steel syndrome and suggest a founder mutation effect in the Puerto Rican population. Eur J Hum Genet 23:342-346.)
Faundes-Banka syndrome (619376)	Víctor Faundes (Chile)	2021	Multi-ancestry	(Faundes et al., 2021Faundes V, Jennings MD, Crilly S, Legraie S, Withers SE, Cuvertino S, Davies SJ, Douglas AGL, Fry AE, Harrison V et al. (2021) Impaired eif5a function causes a Mendelian disorder that is partially rescued in model systems by spermidine. Nat Commun 12:833.)
Radiohumeral fusions with other skeletal and craniofacial anomalies (614416)	Denise P. Cavalcanti (Brazil)	2023	Multi-ancestry	(Silveira et al., 2023Silveira KC, Fonseca IC, Oborn C, Wengryn P, Ghafoor S, Beke A, Dreseris ES, Wong C, Iacovone A, Soltys CL et al. (2023) Cyp26b1-related disorder: Expanding the ends of the spectrum through clinical and molecular evidence. Hum Genet 142:1571-1586.)

[1] Send correspondence to
Víctor Faundes. Universidad de Chile, Instituto de Nutrición y Tecnología de los Alimentos, Laboratorio de Genética y Enfermedades Metabólicas, Avenida El Líbano, 5524, 7830490, Santiago, Chile. E-mail: vfaundes@inta.uchile.cl

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Discovery of novel genetic syndromes in Latin America: Opportunities and challenges

Abstract