Atypical NF1 Microdeletions: Challenges and Opportunities for Genotype/Phenotype Correlations in Patients with Large NF1 Deletions

• Published in: Genes Vol. 12; no. 10; p. 1639
• Main Authors: Kehrer-Sawatzki, Hildegard, Wahlländer, Ute, Cooper, David N, Mautner, Victor-Felix
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.10.2021; MDPI
• Subjects: Age; Autism; Chromosome Deletion; Cognitive ability; Comparative analysis; Female; Gene Deletion; Genetic Association Studies; Genetic disorders; Genotype; Genotype & phenotype; Genotypes; Hemizygosity; Humans; Male; Medical screening; Mutation; Neural coding; Neurofibromatosis; Neurofibromatosis 1 - genetics; Neurofibromatosis 1 - pathology; Neurofibromin 1; Neurofibromin 1 - genetics; Neurological disorders; Patients; Phenotypes; Proteins; Recklinghausen's disease; Review; Software; Tumors; United States > US; Netherlands; SUZ12; NF1 microdeletions; genotype/phenotype correlations; NF1; neurofibromatosis type 1; genodermatosis; CRLF3
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes12101639

Patients with neurofibromatosis type 1 (NF1) and type 1 deletions often exhibit more severe clinical manifestations than patients with intragenic 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 deletions encompass 1.4 Mb and are associated with the loss of 14 protein-coding genes, including and . Atypical deletions, which do not encompass all 14 protein-coding genes located within the type 1 deletion region, have the potential to contribute to the delineation of the genotype/phenotype relationship in patients with microdeletions. Here, we review all atypical 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 deletion of 698 kb which, in addition to the gene, includes five genes located centromeric to . The atypical deletion in this patient does not include the gene but does encompass . Comparative analysis of such atypical deletions suggests that hemizygosity is likely to contribute significantly to the reduced cognitive abilities, severe global developmental delay and facial dysmorphisms observed in patients with type 1 deletions.