{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:58:38Z","timestamp":1792205918603,"version":"4.4.0"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T00:00:00Z","timestamp":1682985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J intellect Disabil Res"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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 <jats:italic>NIPA1<\/jats:italic> and <jats:italic>NIPA2<\/jats:italic> genes, contains a recurrent but rare CNV, flanked by the break points BP1 and BP2. Both BP1\u2013BP2 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\u2010of\u2010origin effect (POE) are some of the mechanisms that have been proposed as an explanation of the wide phenotypic variability. As <jats:italic>NIPA1<\/jats:italic> and <jats:italic>NIPA2<\/jats:italic> encode for proteins that mediate magnesium (Mg<jats:sup>2+<\/jats:sup>) metabolism, it has been suggested that urinary Mg<jats:sup>2+<\/jats:sup> levels could potentially represent informative and affordable biomarkers for a rapid screening of 15q11.2 duplications or deletions. Furthermore, magnesium supplementation has been proposed as possible therapeutic strategy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty one children with ID and\/or other neurodevelopmental disorders carrying either a duplication or a deletion in 15q11.2 BP1\u2013BP2 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<jats:sup>2+<\/jats:sup> levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2010deficit disorder\/attention\u2010deficit 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<jats:sup>2+<\/jats:sup> urinary values, without correlation with 15q11.2 copy numbers. However, the variance of urinary Mg<jats:sup>2+<\/jats:sup> levels largely increases in individuals with 15q11.2 deletion\/duplication.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study provides further evidence that 15q11.2 BP1\u2013BP2 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<jats:sup>2+<\/jats:sup> levels can be used as biomarkers to screen children with neurodevelopmental disorders for 15q11.2 duplication\/deletion. However, there are evidences of correlations between 15q11.2 BP1\u2013BP2 CNV and Mg<jats:sup>2+<\/jats:sup> metabolism and future studies may pave the way to new therapeutic options.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jir.13038","type":"journal-article","created":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T10:44:06Z","timestamp":1683024246000},"page":"679-689","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Clinical features and magnesium levels: Novel insights in 15q11.2 BP1\u2013BP2 copy number variants"],"prefix":"10.1111","volume":"67","author":[{"given":"C.","family":"Meossi","sequence":"first","affiliation":[{"name":"Universit\u00e0 degli Studi di Milano and Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2638-9910","authenticated-orcid":false,"given":"A.","family":"Carrer","sequence":"additional","affiliation":[{"name":"Universit\u00e0 degli Studi di Milano and Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Ciaccio","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience Fondazione IRCCS Istituto Neurologico C. Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Estienne","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience Fondazione IRCCS Istituto Neurologico C. Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0236-7941","authenticated-orcid":false,"given":"R.","family":"Silipigni","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. L.","family":"Sciacca","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pathology and Medical Genetics Fondazione IRCCS Istituto Neurologico C. 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