Short-read whole genome sequencing identifies causative variants in most individuals with previously unexplained aniridia.

Eye Diseases Genetic Testing Mutation

Journal

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

Informations de publication

Date de publication:
30 Nov 2023
Historique:
received: 12 03 2023
accepted: 25 09 2023
medline: 5 12 2023
pubmed: 5 12 2023
entrez: 5 12 2023
Statut: aheadofprint

Résumé

Classic aniridia is a highly penetrant autosomal dominant disorder characterised by congenital absence of the iris, foveal hypoplasia, optic disc anomalies and progressive opacification of the cornea. >90% of cases of classic aniridia are caused by heterozygous, loss-of-function variants affecting the Short-read whole genome sequencing was performed on 51 (39 affected) individuals from 37 different families who had screened negative for mutations in the Likely causative mutations were identified in 22 out of 37 (59%) families. In 19 out of 22 families, the causative genomic changes have an interpretable deleterious impact on the Whole genome sequencing proves to be an effective diagnostic test in most individuals with previously unexplained aniridia.

Sections du résumé

BACKGROUND BACKGROUND
Classic aniridia is a highly penetrant autosomal dominant disorder characterised by congenital absence of the iris, foveal hypoplasia, optic disc anomalies and progressive opacification of the cornea. >90% of cases of classic aniridia are caused by heterozygous, loss-of-function variants affecting the
METHODS METHODS
Short-read whole genome sequencing was performed on 51 (39 affected) individuals from 37 different families who had screened negative for mutations in the
RESULTS RESULTS
Likely causative mutations were identified in 22 out of 37 (59%) families. In 19 out of 22 families, the causative genomic changes have an interpretable deleterious impact on the
CONCLUSION CONCLUSIONS
Whole genome sequencing proves to be an effective diagnostic test in most individuals with previously unexplained aniridia.

Identifiants

pubmed: 38050128
pii: jmg-2023-109181
doi: 10.1136/jmg-2023-109181
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Hildegard Nikki Hall (HN)

Institute of Genetics and Cancer, The University of Edinburgh MRC Human Genetics Unit, Edinburgh, UK nikki.hall@ed.ac.uk.

David Parry (D)

Institute of Genetics and Cancer, The University of Edinburgh MRC Human Genetics Unit, Edinburgh, UK.
Illumina United Kingdom, Edinburgh, UK.

Mihail Halachev (M)

Institute of Genetics and Cancer, The University of Edinburgh MRC Human Genetics Unit, Edinburgh, UK.

Kathleen A Williamson (KA)

Institute of Genetics and Cancer, The University of Edinburgh MRC Human Genetics Unit, Edinburgh, UK.

Kevin Donnelly (K)

Institute of Genetics and Cancer, The University of Edinburgh MRC Human Genetics Unit, Edinburgh, UK.

Jose Campos Parada (J)

Institute of Genetics and Cancer, The University of Edinburgh MRC Human Genetics Unit, Edinburgh, UK.

Shipra Bhatia (S)

Institute of Genetics and Cancer, The University of Edinburgh MRC Human Genetics Unit, Edinburgh, UK.

Jeffrey Joseph (J)

MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, UK.

Simon Holden (S)

East Anglia Regional Genetics Service, Addenbrooke's Hospital, Cambridge, UK.

Trine E Prescott (TE)

Department of Medical Genetics, Telemark Hospital, Skien, Norway.

Pierre Bitoun (P)

Consultations de Génétique médicale, Service de Pédiatrie, CHU Paris-Nord, Hôpital Jean Verdier, Bondy, France.

Edwin P Kirk (EP)

Centre for Clinical Genetics, Sydney Children's Hospital Randwick, Randwick, New South Wales, Australia.

Ruth Newbury-Ecob (R)

Department of Clinical Genetics, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.

Katherine Lachlan (K)

University Hospital Southampton, NHS Foundation Trust Wessex Clinical Genetics Service, Southampton, UK.

Juan Bernar (J)

Department of Genetics, Hospital Ruber Internacional, Madrid, Spain.

Veronica van Heyningen (V)

MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, UK.
Institute of Ophthalmology, University College London, London, UK.

David R FitzPatrick (DR)

Institute of Genetics and Cancer, The University of Edinburgh MRC Human Genetics Unit, Edinburgh, UK.

Alison Meynert (A)

Institute of Genetics and Cancer, The University of Edinburgh MRC Human Genetics Unit, Edinburgh, UK.

Classifications MeSH