Clinical and genetic analysis further delineates the phenotypic spectrum of ALDH1A3-related anophthalmia and microphthalmia.


Journal

European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235

Informations de publication

Date de publication:
10 2023
Historique:
received: 26 08 2022
accepted: 13 03 2023
revised: 30 01 2023
medline: 4 10 2023
pubmed: 31 3 2023
entrez: 30 3 2023
Statut: ppublish

Résumé

Biallelic pathogenic variants in ALDH1A3 are responsible for approximately 11% of recessively inherited cases of severe developmental eye anomalies. Some individuals can display variable neurodevelopmental features, but the relationship to the ALDH1A3 variants remains unclear. Here, we describe seven unrelated families with biallelic pathogenic ALDH1A3 variants: four compound heterozygous and three homozygous. All affected individuals had bilateral anophthalmia/microphthalmia (A/M), three with additional intellectual or developmental delay, one with autism and seizures and three with facial dysmorphic features. This study confirms that individuals with biallelic pathogenic ALDH1A3 variants consistently manifest A/M, but additionally display neurodevelopmental features with significant intra- and interfamilial variability. Furthermore, we describe the first case with cataract and highlight the importance of screening ALDH1A3 variants in nonconsanguineous families with A/M.

Identifiants

pubmed: 36997679
doi: 10.1038/s41431-023-01342-8
pii: 10.1038/s41431-023-01342-8
pmc: PMC10545824
doi:

Substances chimiques

Aldehyde Oxidoreductases EC 1.2.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1175-1180

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2023. The Author(s).

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Auteurs

Yesim Kesim (Y)

Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK.

Fabiola Ceroni (F)

Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK.
Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.

Alejandra Damián (A)

Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain.
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain.

Fiona Blanco-Kelly (F)

Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain.
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain.

Carmen Ayuso (C)

Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain.
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain.

Kathy Williamson (K)

MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.

Véronique Paquis-Flucklinger (V)

Department of Medical Genetics, Nice Teaching Hospital, Nice, France.

Dorine A Bax (DA)

Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK.

Julie Plaisancié (J)

INSERM U1214, ToNIC, Université Toulouse III, Toulouse, France.
Centre de Référence des Affections Rares en Génétique Ophtalmologique CARGO, Site Constitutif, CHU Toulouse, Toulouse, France.

Claudine Rieubland (C)

Department of Human Genetics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Mostafa Chamlal (M)

Department of Pediatrics, RAZI-CLINIC Hospital, Tangier, Morocco.

Marta Cortón (M)

Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain.
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain.

Nicolas Chassaing (N)

Centre de Référence des Affections Rares en Génétique Ophtalmologique CARGO, Site Constitutif, CHU Toulouse, Toulouse, France.

Patrick Calvas (P)

Centre de Référence des Affections Rares en Génétique Ophtalmologique CARGO, Site Constitutif, CHU Toulouse, Toulouse, France.

Nicola K Ragge (NK)

Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK. nragge@brookes.ac.uk.
Department of Clinical Genetics, West Midlands Regional Clinical Genetics Service and Birmingham Health Partners, Birmingham Women's and Children's Foundation Trust, Birmingham, UK. nragge@brookes.ac.uk.

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