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Atypical NF1 microdeletions: challenges and opportunities for Genotype/Phenotype correlations in patients with large NF1 deletions

Kehrer-Sawatzki, Hildegard, Wahlländer, Ute, Cooper, David N. ORCID: https://orcid.org/0000-0002-8943-8484 and Mautner, Victor-Felix 2021. Atypical NF1 microdeletions: challenges and opportunities for Genotype/Phenotype correlations in patients with large NF1 deletions. Genes 12 (10) , 1639. 10.3390/genes12101639

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Abstract

Patients with neurofibromatosis type 1 (NF1) and type 1 NF1 deletions often exhibit more severe clinical manifestations than patients with intragenic NF1 gene mutations, including facial dysmorphic features, overgrowth, severe global developmental delay, severe autistic symptoms and considerably reduced cognitive abilities, all of which are detectable from a very young age. Type 1 NF1 deletions encompass 1.4 Mb and are associated with the loss of 14 protein-coding genes, including NF1 and SUZ12. Atypical NF1 deletions, which do not encompass all 14 protein-coding genes located within the type 1 NF1 deletion region, have the potential to contribute to the delineation of the genotype/phenotype relationship in patients with NF1 microdeletions. Here, we review all atypical NF1 deletions reported to date as well as the clinical phenotype observed in the patients concerned. We compare these findings with those of a newly identified atypical NF1 deletion of 698 kb which, in addition to the NF1 gene, includes five genes located centromeric to NF1. The atypical NF1 deletion in this patient does not include the SUZ12 gene but does encompass CRLF3. Comparative analysis of such atypical NF1 deletions suggests that SUZ12 hemizygosity is likely to contribute significantly to the reduced cognitive abilities, severe global developmental delay and facial dysmorphisms observed in patients with type 1 NF1 deletions.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/)
Publisher: MDPI
ISSN: 2073-4425
Date of First Compliant Deposit: 25 January 2022
Date of Acceptance: 14 October 2021
Last Modified: 19 May 2023 19:32
URI: https://orca.cardiff.ac.uk/id/eprint/146891

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