Nationwide genetic analysis of more than 600 families with inherited eye diseases in Argentina.


Journal

NPJ genomic medicine
ISSN: 2056-7944
Titre abrégé: NPJ Genom Med
Pays: England
ID NLM: 101685193

Informations de publication

Date de publication:
22 May 2023
Historique:
received: 12 12 2022
accepted: 05 04 2023
medline: 23 5 2023
pubmed: 23 5 2023
entrez: 22 5 2023
Statut: epublish

Résumé

This study corresponds to the first large-scale genetic analysis of inherited eye diseases (IED) in Argentina and describes the comprehensive genetic profile of a large cohort of patients. Medical records of 22 ophthalmology and genetics services throughout 13 Argentinian provinces were analyzed retrospectively. Patients with a clinical diagnosis of an ophthalmic genetic disease and a history of genetic testing were included. Medical, ophthalmological and family history was collected. A total of 773 patients from 637 families were included, with 98% having inherited retinal disease. The most common phenotype was retinitis pigmentosa (RP, 62%). Causative variants were detected in 379 (59%) patients. USH2A, RPGR, and ABCA4 were the most common disease-associated genes. USH2A was the most frequent gene associated with RP, RDH12 early-onset severe retinal dystrophy, ABCA4 Stargardt disease, PROM1 cone-rod dystrophy, and BEST1 macular dystrophy. The most frequent variants were RPGR c.1345 C > T, p.(Arg449*) and USH2A c.15089 C > A, p.(Ser5030*). The study revealed 156/448 (35%) previously unreported pathogenic/likely pathogenic variants and 8 possible founder mutations. We present the genetic landscape of IED in Argentina and the largest cohort in South America. This data will serve as a reference for future genetic studies, aid diagnosis, inform counseling, and assist in addressing the largely unmet need for clinical trials to be conducted in the region.

Identifiants

pubmed: 37217489
doi: 10.1038/s41525-023-00352-1
pii: 10.1038/s41525-023-00352-1
pmc: PMC10202926
doi:

Types de publication

Journal Article

Langues

eng

Pagination

8

Subventions

Organisme : Wellcome Trust (Wellcome)
ID : 099173/Z/12/Z
Organisme : Fight for Sight UK
ID : 5045/46

Informations de copyright

© 2023. The Author(s).

Références

Am J Hum Genet. 2000 Jun;66(6):1975-8
pubmed: 10775529
Curr Opin Genet Dev. 2017 Feb;42:33-39
pubmed: 28157586
Am J Med Genet A. 2018 Dec;176(12):2695-2703
pubmed: 30513137
Dis Model Mech. 2021 Dec 1;14(12):
pubmed: 34935906
Ophthalmic Genet. 2022 Aug;43(4):438-445
pubmed: 35272565
J Hum Genet. 2011 Jul;56(7):484-90
pubmed: 21593743
Nat Commun. 2016 Nov 24;7:13637
pubmed: 27882922
Mol Vis. 2010 Dec 03;16:2550-8
pubmed: 21151602
Am J Med Genet C Semin Med Genet. 2020 Sep;184(3):753-761
pubmed: 32856789
Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2709-13
pubmed: 18515597
Genes (Basel). 2020 Jan 16;11(1):
pubmed: 31963381
PLoS One. 2014 Jan 15;9(1):e85752
pubmed: 24454928
N Engl J Med. 2021 Nov 11;385(20):1868-1880
pubmed: 34758253
J Neuroophthalmol. 2021 Sep 1;41(3):e290-e292
pubmed: 33136666
J Gynecol Oncol. 2019 Jul;30(4):e60
pubmed: 31074248
J Med Genet. 2016 Nov;53(11):761-767
pubmed: 27208204
J Fr Ophtalmol. 2016 Mar;39(3):277-86
pubmed: 26868535
Genet Med. 2009 Sep;11(9):655-62
pubmed: 19752639
Hum Genet. 2022 Nov;141(11):1723-1738
pubmed: 35226187
Am J Hum Genet. 2017 Feb 2;100(2):334-342
pubmed: 28132693
Nat Genet. 2014 Aug;46(8):818-25
pubmed: 24974849
Sci Rep. 2021 Jan 15;11(1):1526
pubmed: 33452396
Biomed Res Int. 2015;2015:461524
pubmed: 25874212
Ophthalmology. 2017 Sep;124(9):1314-1331
pubmed: 28559085
J Med Genet. 2010 Jul;47(7):499-506
pubmed: 20507924
Br J Ophthalmol. 2022 Aug 29;:
pubmed: 36038193
Nat Genet. 2006 Nov;38(11):1242-4
pubmed: 17013395
Invest Ophthalmol Vis Sci. 2021 Feb 1;62(2):13
pubmed: 33576794
Genes (Basel). 2018 Jul 19;9(7):
pubmed: 30029497
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
J Med Genet. 2012 Jan;49(1):27-36
pubmed: 22135276
Genet Med. 2015 Apr;17(4):271-8
pubmed: 25356976
Hum Mutat. 2020 Sep;41(9):1514-1527
pubmed: 32531858
Br J Ophthalmol. 2017 Sep;101(9):1147-1154
pubmed: 28689169
Ophthalmic Genet. 2018 Jan-Feb;39(1):73-79
pubmed: 28945494
Cell. 2019 Jan 24;176(3):535-548.e24
pubmed: 30661751
PLoS Genet. 2009 Jan;5(1):e1000360
pubmed: 19180233
Invest Ophthalmol Vis Sci. 2009 Mar;50(3):1058-64
pubmed: 19060277
Mol Vis. 2021 Jul 16;27:457-465
pubmed: 34321860
Ophthalmology. 2020 Oct;127(10):1384-1394
pubmed: 32423767
Am J Med Genet C Semin Med Genet. 2020 Sep;184(3):828-837
pubmed: 32893963
Am J Med Genet C Semin Med Genet. 2020 Sep;184(3):728-752
pubmed: 32865313
Ophthalmology. 2022 Oct;129(10):e89-e113
pubmed: 36058735
Clin Chim Acta. 2001 Nov;313(1-2):209-15
pubmed: 11694261
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
PLoS Genet. 2015 Dec 04;11(12):e1005602
pubmed: 26636962
Sci Rep. 2021 Oct 18;11(1):20607
pubmed: 34663891
Mol Vis. 2014 Feb 07;20:178-82
pubmed: 24520187
Nat Rev Genet. 2018 Mar;19(3):175-185
pubmed: 29151588
NPJ Genom Med. 2021 Feb 19;6(1):16
pubmed: 33608557
PLoS One. 2020 Jul 16;15(7):e0233808
pubmed: 32673320
Genes (Basel). 2021 Nov 19;12(11):
pubmed: 34828430
Invest Ophthalmol Vis Sci. 2011 Aug 05;52(9):6206-12
pubmed: 21330655
Am J Hum Genet. 2016 Oct 6;99(4):877-885
pubmed: 27666373
Orphanet J Rare Dis. 2022 May 12;17(1):197
pubmed: 35551639
Nat Methods. 2014 Apr;11(4):361-2
pubmed: 24681721
Am J Hum Genet. 2004 Jan;74(1):128-38
pubmed: 14681825
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
PLoS One. 2018 May 1;13(5):e0196325
pubmed: 29715266
Science. 2010 May 7;328(5979):710-722
pubmed: 20448178
Am J Hum Genet. 2017 Jan 5;100(1):75-90
pubmed: 28041643
Br J Ophthalmol. 2017 Jan;101(1):25-30
pubmed: 27491360
PLoS One. 2012;7(4):e34695
pubmed: 22506044
Am J Hum Genet. 2002 Jun;70(6):1545-54
pubmed: 11992260
Br J Ophthalmol. 2022 Apr;106(4):445-451
pubmed: 33712480
Nat Rev Genet. 2020 Apr;21(4):243-254
pubmed: 32034321
Mol Genet Genomic Med. 2021 Dec;9(12):e1663
pubmed: 33749171
Genome Res. 2010 Jan;20(1):110-21
pubmed: 19858363
Ophthalmology. 2016 May;123(5):1143-50
pubmed: 26872967
BMC Med Genomics. 2021 Mar 10;14(1):74
pubmed: 33691693
JAMA. 2005 Apr 13;293(14):1783-5
pubmed: 15827320
Eur J Med Genet. 2008 May-Jun;51(3):183-96
pubmed: 18276201
Nat Genet. 2000 Jul;25(3):289-93
pubmed: 10888875
Am J Hum Genet. 2011 May 13;88(5):643-9
pubmed: 21549338

Auteurs

Patricio G Schlottmann (PG)

Charles Centro Oftalmológico, Buenos Aires, Argentina.

José D Luna (JD)

Centro Privado de Ojos Romagosa SA, Córdoba, Argentina.

Natalia Labat (N)

Centro Privado de Ojos Romagosa SA, Córdoba, Argentina.

María Belén Yadarola (MB)

Centro Privado de Ojos Romagosa SA, Córdoba, Argentina.

Silvina Bainttein (S)

Instituto Oftalmológico de Córdoba, Córdoba, Argentina.

Evangelina Esposito (E)

University Clinic Reina Fabiola, Córdoba, Córdoba, Argentina.
Catholic University of Cordoba, Cordoba, Argentina.

Agustina Ibañez (A)

University Clinic Reina Fabiola, Córdoba, Córdoba, Argentina.
Catholic University of Cordoba, Cordoba, Argentina.

Evangelina Ivón Barbaro (EI)

Hospital Provincial Neuquén, Neuquén, Argentina.

Alejandro Álvarez Mendiara (A)

Instituto Oftalmológico Cortina, Santa Rosa, La Pampa, Argentina.

Carolina P Picotti (CP)

Centro Médico Lisandro de la Torre, Villa María, Córdoba, Argentina.

Andrea Chirino Misisian (A)

Centro Médico Lisandro de la Torre, Villa María, Córdoba, Argentina.

Luciana Andreussi (L)

Clínica de la Visión, San Juan, Argentina.

Julieta Gras (J)

Centrovision Mendoza SA, Mendoza, Argentina.

Luciana Capalbo (L)

Hospital MJ Becker, La Punta, San Luis, Argentina.

Mauro Visotto (M)

Instituto Oftalmológico Trelew, Trelew, Chubut, Argentina.

José E Dipierri (JE)

Universidad Nacional de Jujuy, Jujuy, Argentina.

Emilio Alcoba (E)

Hospital Materno Infantil Dr Héctor Quintana, Jujuy, Argentina.

Laura Fernández Gabrielli (L)

Nuevo Hospital San Antonio de Padua, Río Cuarto, Córdoba, Argentina.

Silvia Ávila (S)

Facultad de Ciencias Médicas, Universidad Nacional del Comahue, Río Negro, Argentina.

María Emilia Aucar (ME)

Instituto de Ojos y Oídos, Resistencia, Chaco, Argentina.

Daniel M Martin (DM)

Instituto de Ojos y Oídos, Resistencia, Chaco, Argentina.

Gerardo Juan Ormaechea (GJ)

Clínica de Ojos Córdoba, Córdoba, Argentina.

M Eugenia Inga (ME)

Organización Medica de Investigación, Buenos Aires, Argentina.

Aníbal A Francone (AA)

Charles Centro Oftalmológico, Buenos Aires, Argentina.

Martin Charles (M)

Charles Centro Oftalmológico, Buenos Aires, Argentina.

Tamara Zompa (T)

Charles Centro Oftalmológico, Buenos Aires, Argentina.

Pablo Javier Pérez (PJ)

, Santiago del Estero, Argentina.

Vanesa Lotersztein (V)

Centro Nacional de Genética Médica, Buenos Aires, Argentina.

Pedro J Nuova (PJ)

Ocularyb Oftalmoclinica, Yerba Buena, Tucumán, Argentina.

Ivana B Canonero (IB)

Hospital Privado Universitario de Córdoba, Córdoba, Argentina.

Omar A Mahroo (OA)

Moorfields Eye Hospital, London, UK.
UCL Institute of Ophthalmology, University College London, London, UK.

Michel Michaelides (M)

Moorfields Eye Hospital, London, UK.
UCL Institute of Ophthalmology, University College London, London, UK.

Gavin Arno (G)

Moorfields Eye Hospital, London, UK.
UCL Institute of Ophthalmology, University College London, London, UK.

Malena Daich Varela (M)

Moorfields Eye Hospital, London, UK. m.daichvarela@ucl.ac.uk.
UCL Institute of Ophthalmology, University College London, London, UK. m.daichvarela@ucl.ac.uk.

Classifications MeSH