Article ; Online: Clinical features and magnesium levels: Novel insights in 15q11.2 BP1-BP2 copy number variants.
Journal of intellectual disability research : JIDR
2023 Volume 67, Issue 7, Page(s) 679–689
Abstract: Background: Investigating copy number variations (CNVs) such as microdeletions or microduplications can significantly contribute to discover the aetiology of neurodevelopmental disorders. 15q11.2 genomic region, including NIPA1 and NIPA2 genes, contains ...
| Abstract | Background: Investigating copy number variations (CNVs) such as microdeletions or microduplications can significantly contribute to discover the aetiology of neurodevelopmental disorders. 15q11.2 genomic region, including NIPA1 and NIPA2 genes, contains a recurrent but rare CNV, flanked by the break points BP1 and BP2. Both BP1-BP2 microdeletion and microduplication have been associated with intellectual disability (ID), neuropsychiatric/behavioural disturbances and mild clinical features, even if with incomplete penetrance and variable expressivity. The pathogenic role of this CNV is quite unclear though. Unknown variants in other DNA regions and parent-of-origin effect (POE) are some of the mechanisms that have been proposed as an explanation of the wide phenotypic variability. As NIPA1 and NIPA2 encode for proteins that mediate magnesium (Mg Methods: Thirty one children with ID and/or other neurodevelopmental disorders carrying either a duplication or a deletion in 15q11.2 BP1-BP2 region have been recruited. When available, blood samples from parents have been analysed to identify the CNV origin. All participants underwent family and medical data collection, physical examination and neuropsychiatric assessment. Electroencephalogram (EEG) and brain magnetic resonance imaging (MRI) scan were performed in 15 children. In addition, 11 families agreed to participate to the assessment of blood and urinary Mg Results: We observed a highly variable phenotypic spectrum of developmental issues encompassing ID in most subjects as well as a variety of behavioural disorders such as autism and attention-deficit disorder/attention-deficit hyperactivity disorder. Dysmorphic traits and malformations were detected only in a minority of the participants, and no clear association with growth anomalies was found. Abnormal brain MRI and/or EEG were reported respectively in 64% and 92% of the subjects. Inheritance assessment highlighted an excess of duplication of maternal origin, while cardiac alterations were detected only in children with 15q11.2 CNV inherited from the father. We found great variability in Mg Conclusions: This study provides further evidence that 15q11.2 BP1-BP2 CNV is associated with a broad spectrum of neurodevelopmental disorders and POE might be an explanation for clinical variability. However, some issues may question the real impact of 15q11.2 CNV on the phenotype in the carriers: DNA sequencing could be useful to exclude other pathogenic gene mutations. Our results do not support the possibility that urinary Mg |
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| MeSH term(s) | Humans ; Chromosome Aberrations ; Magnesium ; DNA Copy Number Variations/genetics ; Neurodevelopmental Disorders/genetics ; Intellectual Disability/genetics ; Biomarkers |
| Chemical Substances | Magnesium (I38ZP9992A) ; Biomarkers |
| Language | English |
| Publishing date | 2023-05-02 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 1103832-9 |
| ISSN | 1365-2788 ; 0964-2633 |
| ISSN (online) | 1365-2788 |
| ISSN | 0964-2633 |
| DOI | 10.1111/jir.13038 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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