Clinical, genetic and biochemical signatures of

Eye Diseases Genetics, Medical Human Genetics Inheritance Patterns Ophthalmology

Journal

Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R

Informations de publication

Date de publication:
16 Aug 2023
Historique:
received: 12 04 2023
accepted: 16 07 2023
medline: 17 8 2023
pubmed: 17 8 2023
entrez: 16 8 2023
Statut: aheadofprint

Résumé

The retinoic acid (RA) pathway plays a crucial role in both eye morphogenesis and the visual cycle. Individuals with monoallelic and biallelic pathogenic variants in We report here seven new families (13 patients) with isolated and syndromic MAC harbouring heterozygous For the first time, malformations that overlap the clinical spectrum of vitamin A deficiency are reported, providing a link with other RA disorders. Our data support two distinct phenotypes, depending on the nature and mode of inheritance of the variants: dominantly inherited, almost exclusively missense, associated with ocular malformations, in contrast to recessive, mainly truncating, associated with retinal degeneration. Moreover, we also confirm the skewed inheritance and impact of maternal Dominant missense variants in

Sections du résumé

BACKGROUND BACKGROUND
The retinoic acid (RA) pathway plays a crucial role in both eye morphogenesis and the visual cycle. Individuals with monoallelic and biallelic pathogenic variants in
METHODS METHODS
We report here seven new families (13 patients) with isolated and syndromic MAC harbouring heterozygous
RESULTS RESULTS
For the first time, malformations that overlap the clinical spectrum of vitamin A deficiency are reported, providing a link with other RA disorders. Our data support two distinct phenotypes, depending on the nature and mode of inheritance of the variants: dominantly inherited, almost exclusively missense, associated with ocular malformations, in contrast to recessive, mainly truncating, associated with retinal degeneration. Moreover, we also confirm the skewed inheritance and impact of maternal
CONCLUSION CONCLUSIONS
Dominant missense variants in

Identifiants

pubmed: 37586836
pii: jmg-2023-109331
doi: 10.1136/jmg-2023-109331
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Julie Plaisancié (J)

Laboratoire National de Référence (LBMR), Génétique des anomalies malformatives de l'œil, CHU Toulouse, Toulouse, France plaisancie.j@chu-toulouse.fr.
Unité ToNIC Inserm 1214, CHU Toulouse, Toulouse, France.
Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), CHU Toulouse, Toulouse, France.

Jelena Martinovic (J)

Département de Génétique, Unité de Fœtopathologie, Hopital Necker-Enfants Malades, Paris, France.

Bertrand Chesneau (B)

Laboratoire National de Référence (LBMR), Génétique des anomalies malformatives de l'œil, CHU Toulouse, Toulouse, France.
Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), CHU Toulouse, Toulouse, France.

Sandra Whalen (S)

Genetique Medicale, Hopital Armand-Trousseau, Paris, France.

Diana Rodriguez (D)

Département de Génétique, Hôpitaux Universitaires Paris Ile-de-France Ouest, Paris, France.

Séverine Audebert-Bellanger (S)

Service de Génétique Médicale, CHU Brest, Brest, France.

Pauline Marzin (P)

Fédération de Génétique et Médecine Génomique, Service de Médecine Génomique des Maladies Rares, Necker-Enfants Malades Hospitals, Paris, France.

Sarah Grotto (S)

Maternité Port-Royal, FHU PREMA, Hôpital Cochin, Paris, France.

Isabelle Perthus (I)

Centre d'Etude des Malformations Congénitales en Auvergne, Génétique Médicale, CHU Estaing, Clermont-Ferrand, France.

Richard James Holt (RJ)

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

Dorine A Bax (DA)

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

Nicola Ragge (N)

Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK.
West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.

Nicolas Chassaing (N)

Laboratoire National de Référence (LBMR), Génétique des anomalies malformatives de l'œil, CHU Toulouse, Toulouse, France.
Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), CHU Toulouse, Toulouse, France.

Classifications MeSH