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A severe case of Bosch–Boonstra–Schaaf optic atrophy syndrome with a novel description of coloboma and septo‐optic dysplasia, owing to a start codon variant in the NR2F1 gene

A severe case of Bosch–Boonstra–Schaaf optic atrophy syndrome with a novel description of coloboma and septo‐optic dysplasia, owing to a start codon variant in the NR2F1 gene
A severe case of Bosch–Boonstra–Schaaf optic atrophy syndrome with a novel description of coloboma and septo‐optic dysplasia, owing to a start codon variant in the NR2F1 gene

Bosch–Boonstra–Schaaf optic atrophy syndrome (BBSOAS) is a rare congenital syndrome characterized by a range of phenotypes including optic atrophy and intellectual disability among other features. Pathogenic variants in the NR2F1 (nuclear receptor subfamily 2 group F member 1) gene have been linked to this condition. A recent report has shown that pathogenic variants in the start codon lead to decreased expression of the NR2F1 protein and a relatively mild phenotype, similar to that seen in whole gene deletions, and due to the lack of the dominant negative effect. Here we describe a severe case of BBSOAS with an initiation codon missense variant. The developmental delay, seizures, optic atrophy are in keeping with features observed in this condition, however this is the first report to describe colobomas and septo-optic dysplasia as associated features potentially extending the phenotype linked to BBSOAS. In addition, this is the first description of a severe phenotype linked to a de novo missense variant in the start codon of the NR2F1 gene.

Bosch–Boonstra–Schaaf optic atrophy syndrome, NR2F1, coloboma, intellectual disability, septo-optic dysplasia
1552-4825
900-906
Gazdagh, Gabriella
58d84505-107d-4279-9816-fa285b9082ca
Mawby, Rebecca
18a4197c-0a76-4129-a1a0-6747809aace5
Self, Jay E.
0f6efc58-ae24-4667-b8d6-6fafa849e389
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91
Gazdagh, Gabriella
58d84505-107d-4279-9816-fa285b9082ca
Mawby, Rebecca
18a4197c-0a76-4129-a1a0-6747809aace5
Self, Jay E.
0f6efc58-ae24-4667-b8d6-6fafa849e389
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91

Gazdagh, Gabriella, Mawby, Rebecca, Self, Jay E. and Baralle, Diana (2021) A severe case of Bosch–Boonstra–Schaaf optic atrophy syndrome with a novel description of coloboma and septo‐optic dysplasia, owing to a start codon variant in the NR2F1 gene. American Journal of Medical Genetics part A, 188 (3), 900-906. (doi:10.1002/ajmg.a.62569).

Record type: Article

Abstract

Bosch–Boonstra–Schaaf optic atrophy syndrome (BBSOAS) is a rare congenital syndrome characterized by a range of phenotypes including optic atrophy and intellectual disability among other features. Pathogenic variants in the NR2F1 (nuclear receptor subfamily 2 group F member 1) gene have been linked to this condition. A recent report has shown that pathogenic variants in the start codon lead to decreased expression of the NR2F1 protein and a relatively mild phenotype, similar to that seen in whole gene deletions, and due to the lack of the dominant negative effect. Here we describe a severe case of BBSOAS with an initiation codon missense variant. The developmental delay, seizures, optic atrophy are in keeping with features observed in this condition, however this is the first report to describe colobomas and septo-optic dysplasia as associated features potentially extending the phenotype linked to BBSOAS. In addition, this is the first description of a severe phenotype linked to a de novo missense variant in the start codon of the NR2F1 gene.

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Accepted/In Press date: 2 November 2021
e-pub ahead of print date: 17 November 2021
Published date: 17 November 2021
Additional Information: Funding Information: The authors would like to thank the family for their involvement and also the DDD Study team for their contribution. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant no. HICF‐1009‐003). This study makes use of DECIPHER ( http://decipher.sanger.ac.uk ), which is funded by the Wellcome Trust. Please refer to Nature PMID: 25533962 or www.ddduk.org/access.html for full acknowledgment. Publisher Copyright: © 2021 Wiley Periodicals LLC. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
Keywords: Bosch–Boonstra–Schaaf optic atrophy syndrome, NR2F1, coloboma, intellectual disability, septo-optic dysplasia

Identifiers

Local EPrints ID: 453173
URI: http://eprints.soton.ac.uk/id/eprint/453173
ISSN: 1552-4825
PURE UUID: 39fa6f5a-2453-4438-a03a-64046ddfc95d
ORCID for Jay E. Self: ORCID iD orcid.org/0000-0002-1030-9963
ORCID for Diana Baralle: ORCID iD orcid.org/0000-0003-3217-4833

Catalogue record

Date deposited: 10 Jan 2022 17:56
Last modified: 02 Nov 2022 05:01

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Contributors

Author: Gabriella Gazdagh
Author: Rebecca Mawby
Author: Jay E. Self ORCID iD
Author: Diana Baralle ORCID iD

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