Duplication at 19q13.32q13.33 Segregating with Neuropsychiatric Phenotype in a Three-Generation Family: Towards the Definition of a Critical Region
Chromosomal submicroscopic imbalances represent well-known causes of neurodevelopmental disorders. In some cases, these can cause specific autosomal dominant syndromes, with high-to-complete penetrance and de novo occurrence of the variant. In other cases, they result in non-syndromic neurodevelopme...
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MDPI AG
2023-11-01
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| author | Daniele Guadagnolo Gioia Mastromoro Barbara Torres Enrica Marchionni Francesca di Palma Marina Goldoni Dario Cocciadiferro Antonio Novelli Laura Bernardini Antonio Pizzuti |
| author_facet | Daniele Guadagnolo Gioia Mastromoro Barbara Torres Enrica Marchionni Francesca di Palma Marina Goldoni Dario Cocciadiferro Antonio Novelli Laura Bernardini Antonio Pizzuti |
| author_sort | Daniele Guadagnolo |
| collection | DOAJ |
| description | Chromosomal submicroscopic imbalances represent well-known causes of neurodevelopmental disorders. In some cases, these can cause specific autosomal dominant syndromes, with high-to-complete penetrance and de novo occurrence of the variant. In other cases, they result in non-syndromic neurodevelopmental disorders, often acting as moderate-penetrance risk factors, possibly inherited from unaffected parents. We describe a three-generation family with non-syndromic neuropsychiatric features segregating with a novel 19q13.32q13.33 microduplication. The propositus was a 28-month-old male ascertained for psychomotor delay, with no dysmorphic features or malformations. His mother had Attention-Deficit/Hyperactivity Disorder and a learning disability. The maternal uncle had an intellectual disability. Chromosomal microarray analysis identified a 969 kb 19q13.32q13.33 microduplication in the proband. The variant segregated in the mother, the uncle, and the maternal grandmother of the proband, who also presented neuropsychiatric disorders. Fragile-X Syndrome testing was negative. Exome Sequencing did not identify Pathogenic/Likely Pathogenic variants. Imbalances involving 19q13.32 and 19q13.33 are associated with neurodevelopmental delay. A review of the reported microduplications allowed to propose <i>BICRA</i> (MIM *605690) and <i>KPTN</i> (MIM *615620) as candidates for the neurodevelopmental delay susceptibility in 19q13.32q13.33 copy number gains. The peculiarities of this case are the small extension of the duplication, the three-generation segregation, and the full penetrance of the phenotype. |
| first_indexed | 2024-03-08T20:44:23Z |
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| last_indexed | 2024-03-08T20:44:23Z |
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| series | Genes |
| spelling | doaj.art-06e6ae9c205f472abaa095694479a3322023-12-22T14:11:08ZengMDPI AGGenes2073-44252023-11-011412215710.3390/genes14122157Duplication at 19q13.32q13.33 Segregating with Neuropsychiatric Phenotype in a Three-Generation Family: Towards the Definition of a Critical RegionDaniele Guadagnolo0Gioia Mastromoro1Barbara Torres2Enrica Marchionni3Francesca di Palma4Marina Goldoni5Dario Cocciadiferro6Antonio Novelli7Laura Bernardini8Antonio Pizzuti9Department of Experimental Medicine, School of Medicine and Dentistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyDepartment of Experimental Medicine, School of Medicine and Dentistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyMedical Genetics Unit, Department of Diagnosis, Treatment and Transfusional Medicine Services, Fondazione Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carattere Scientifico, 71013 San Giovanni Rotondo (FG), ItalyDepartment of Experimental Medicine, School of Medicine and Dentistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyDepartment of Experimental Medicine, School of Medicine and Dentistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyMedical Genetics Unit, Department of Diagnosis, Treatment and Transfusional Medicine Services, Fondazione Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carattere Scientifico, 71013 San Giovanni Rotondo (FG), ItalyLaboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, ItalyLaboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, ItalyMedical Genetics Unit, Department of Diagnosis, Treatment and Transfusional Medicine Services, Fondazione Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carattere Scientifico, 71013 San Giovanni Rotondo (FG), ItalyDepartment of Experimental Medicine, School of Medicine and Dentistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyChromosomal submicroscopic imbalances represent well-known causes of neurodevelopmental disorders. In some cases, these can cause specific autosomal dominant syndromes, with high-to-complete penetrance and de novo occurrence of the variant. In other cases, they result in non-syndromic neurodevelopmental disorders, often acting as moderate-penetrance risk factors, possibly inherited from unaffected parents. We describe a three-generation family with non-syndromic neuropsychiatric features segregating with a novel 19q13.32q13.33 microduplication. The propositus was a 28-month-old male ascertained for psychomotor delay, with no dysmorphic features or malformations. His mother had Attention-Deficit/Hyperactivity Disorder and a learning disability. The maternal uncle had an intellectual disability. Chromosomal microarray analysis identified a 969 kb 19q13.32q13.33 microduplication in the proband. The variant segregated in the mother, the uncle, and the maternal grandmother of the proband, who also presented neuropsychiatric disorders. Fragile-X Syndrome testing was negative. Exome Sequencing did not identify Pathogenic/Likely Pathogenic variants. Imbalances involving 19q13.32 and 19q13.33 are associated with neurodevelopmental delay. A review of the reported microduplications allowed to propose <i>BICRA</i> (MIM *605690) and <i>KPTN</i> (MIM *615620) as candidates for the neurodevelopmental delay susceptibility in 19q13.32q13.33 copy number gains. The peculiarities of this case are the small extension of the duplication, the three-generation segregation, and the full penetrance of the phenotype.https://www.mdpi.com/2073-4425/14/12/2157neurodevelopmental delay<i>BICRA</i><i>KPTN</i>copy number gain19q13.32q13.33 microduplicationchromosomal microarray analysis |
| spellingShingle | Daniele Guadagnolo Gioia Mastromoro Barbara Torres Enrica Marchionni Francesca di Palma Marina Goldoni Dario Cocciadiferro Antonio Novelli Laura Bernardini Antonio Pizzuti Duplication at 19q13.32q13.33 Segregating with Neuropsychiatric Phenotype in a Three-Generation Family: Towards the Definition of a Critical Region Genes neurodevelopmental delay <i>BICRA</i> <i>KPTN</i> copy number gain 19q13.32q13.33 microduplication chromosomal microarray analysis |
| title | Duplication at 19q13.32q13.33 Segregating with Neuropsychiatric Phenotype in a Three-Generation Family: Towards the Definition of a Critical Region |
| title_full | Duplication at 19q13.32q13.33 Segregating with Neuropsychiatric Phenotype in a Three-Generation Family: Towards the Definition of a Critical Region |
| title_fullStr | Duplication at 19q13.32q13.33 Segregating with Neuropsychiatric Phenotype in a Three-Generation Family: Towards the Definition of a Critical Region |
| title_full_unstemmed | Duplication at 19q13.32q13.33 Segregating with Neuropsychiatric Phenotype in a Three-Generation Family: Towards the Definition of a Critical Region |
| title_short | Duplication at 19q13.32q13.33 Segregating with Neuropsychiatric Phenotype in a Three-Generation Family: Towards the Definition of a Critical Region |
| title_sort | duplication at 19q13 32q13 33 segregating with neuropsychiatric phenotype in a three generation family towards the definition of a critical region |
| topic | neurodevelopmental delay <i>BICRA</i> <i>KPTN</i> copy number gain 19q13.32q13.33 microduplication chromosomal microarray analysis |
| url | https://www.mdpi.com/2073-4425/14/12/2157 |
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