Abstract
The 15q11.2 breakpoint (BP) 1–BP2 deletion syndrome is emerging as the most frequent pathogenic copy number variation in humans related to neurodevelopmental diseases, with changes in cognition, behavior, and brain morphology. Previous publications have reported that patients with 15q11.2 BP1–BP2 deletion showed intellectual disability (ID), speech impairment, developmental delay (DD), and/or behavioral problems. We describe three new cases, aged 3 or 6 years old and belonging to three unrelated Korean families, with a 350-kb 15q11.2 BP1–BP2 deletion of four highly conserved genes, namely, the TUBGCP5, CYFIP1, NIPA2, and NIPA1 genes. All of our cases presented with global DD and/or ID, and the severity ranged from mild to severe, but common facial dysmorphism and congenital malformations in previous reports were not characteristic. The 15q11.2 BP1–BP2 deletion was inherited from an unaffected parent in all cases. Our three cases, together with previous findings from the literature review, confirm some of the features earlier reported to be associated with 15q11.2 BP1–BP2 deletion and help to further delineate the phenotype associated with 15q11.2 deletion. Identification of more cases with 15q11.2 BP1–BP2 deletion will allow us to obtain a better understanding of the clinical phenotypes. Further explanation of the functions of the genes within the 15q11.2 BP1–BP2 region is required to resolve the pathogenic effects on neurodevelopment.
Highlights
The proximal long arm of chromosome 15 is a region rich in segmental duplications that houses five breakpoints (BPs) for recurrent 15q copy number variations (CNVs) as defined by non-allelic homologous recombination
The 15q11.2 BP1–BP2 deletion (Burnside–Butler) syndrome is emerging as the most frequent pathogenic CNV in humans related to neurodevelopmental diseases, with changes in cognition, behavior, and brain morphology [3]
BP1–BP2 deletion and help to further delineate the phenotype associated with 15q11.2 deletion
Summary
The proximal long arm of chromosome 15 is a region rich in segmental duplications that houses five breakpoints (BPs) for recurrent 15q copy number variations (CNVs) as defined by non-allelic homologous recombination. Microdeletions extending from BP1 to BP3 (type 1) or from imprinted region BP2 to BP3 (type 2) cause Prader–Willi syndrome/Angelman syndrome (PWS/AS), depending on the parental origin of the deleted allele [1]. The 15q13.3 microdeletion between BP4 and BP5, which constitutes the CHRNA7 gene, causes mild to moderate intellectual disability (ID) associated with epilepsy with various phenotypes [2]. The 15q11.2 BP1–BP2 deletion (Burnside–Butler) syndrome is emerging as the most frequent pathogenic CNV in humans related to neurodevelopmental diseases, with changes in cognition, behavior, and brain morphology [3]. Previous publications have reported that patients with the 15q11.2 BP1–BP2 deletion showed learning disabilities, speech impairment, developmental delay (DD), and/or behavioral problems [4,5,6,7]. Due to the various phenotypes, it is difficult to provide genetic counselling to families with the
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