Identification of genetic causes of congenital neurodevelopmental disorders using genome wide molecular technologies
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| Formato: | Artículo científico |
| Lenguaje: | en |
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Vilniaus Universitetas
2016
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| _version_ | 1876464058992951296 |
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| author | Eglė Preikšaitienė |
| author_facet | Eglė Preikšaitienė |
| contents | Identification of genetic causes of congenital neurodevelopmental disorders using genome wide molecular technologies Eglė Preikšaitienė Laima Ambrozaitytė Živilė Maldžienė Aušra Morkūnienė Loreta Cimbalistienė Tautvydas Rančelis Algirdas Utkus Vaidutis Kučinskas Medicina CGH array developmental delay whole exome sequencing Intellectual disability Background. Intellectual disability affects about 1–2% of the general population worldwide, and this is the leading socio-economic problem of health care. T he evaluation of the genetic causes of intellectual disability is challenging because these conditions are genetically heterogeneous with many different genetic alterations resulting in clinically indistinguishable phenotypes. Genome wide molecular technologies are effective in a research setting for establishing the new genetic basis of a disease. We describe the first Lithuanian experience in genome-wide CNV detection and whole exome sequencing, presenting the results obtained in the research project UNIGENE. Materials and methods. The patients with developmental delay/intellectual disability have been investigated (n = 66). Diagnostic screening was performed using array-CGH technology. FISH and real time-PCR were used for the confirmation of gene-dose imbalances and investigation of parental samples. Whole exome sequencing using the next generation high throughput NGS technique was used to sequence the samples of 12 selected families. Results. 14 out of 66 patients had pathogenic copy number variants, and one patient had novel likely pathogenic aberration (microdeletion at 4p15.2). Twelve families have been processed for whole exome sequencing. Two identified sequence variants could be classified as pathogenic (in MECP2, CREBBP genes). The other families had several candidate intellectual disability gene variants that are of unclear clinical significance and must be further investigated for possible effect on the molecular pathways of intellectual disability. Conclusions. The genetic heterogeneity of intellectual disability requires genome wide approaches, including detection of chromosomal aberrations by chromosomal microarrays and whole exome sequencing capable of uncovering single gene mutations. This study demonstrates the benefits and challenges that accompany the use of genome wide molecular technologies and provides genotype-phenotype information on 32 patients with chromosomal imbalances and ID candidate sequence variants. 2016 artículo científico 2029-4174 https://www.redalyc.org/articulo.oa?id=694073988004 en http://www.redalyc.org/revista.oa?id=6940 Acta medica Lituanica application/pdf Vilniaus Universitetas Acta medica Lituanica (Lituania) Num.2 Vol.23 |
| format | Artículo científico |
| id | redalyc_694073988004 |
| institution | Redalyc |
| language | en |
| publishDate | 2016 |
| publisher | Vilniaus Universitetas |
| spellingShingle | Identification of genetic causes of congenital neurodevelopmental disorders using genome wide molecular technologies Eglė Preikšaitienė Medicina CGH array developmental delay whole exome sequencing Intellectual disability Identification of genetic causes of congenital neurodevelopmental disorders using genome wide molecular technologies Eglė Preikšaitienė Laima Ambrozaitytė Živilė Maldžienė Aušra Morkūnienė Loreta Cimbalistienė Tautvydas Rančelis Algirdas Utkus Vaidutis Kučinskas Medicina CGH array developmental delay whole exome sequencing Intellectual disability Background. Intellectual disability affects about 1–2% of the general population worldwide, and this is the leading socio-economic problem of health care. T he evaluation of the genetic causes of intellectual disability is challenging because these conditions are genetically heterogeneous with many different genetic alterations resulting in clinically indistinguishable phenotypes. Genome wide molecular technologies are effective in a research setting for establishing the new genetic basis of a disease. We describe the first Lithuanian experience in genome-wide CNV detection and whole exome sequencing, presenting the results obtained in the research project UNIGENE. Materials and methods. The patients with developmental delay/intellectual disability have been investigated (n = 66). Diagnostic screening was performed using array-CGH technology. FISH and real time-PCR were used for the confirmation of gene-dose imbalances and investigation of parental samples. Whole exome sequencing using the next generation high throughput NGS technique was used to sequence the samples of 12 selected families. Results. 14 out of 66 patients had pathogenic copy number variants, and one patient had novel likely pathogenic aberration (microdeletion at 4p15.2). Twelve families have been processed for whole exome sequencing. Two identified sequence variants could be classified as pathogenic (in MECP2, CREBBP genes). The other families had several candidate intellectual disability gene variants that are of unclear clinical significance and must be further investigated for possible effect on the molecular pathways of intellectual disability. Conclusions. The genetic heterogeneity of intellectual disability requires genome wide approaches, including detection of chromosomal aberrations by chromosomal microarrays and whole exome sequencing capable of uncovering single gene mutations. This study demonstrates the benefits and challenges that accompany the use of genome wide molecular technologies and provides genotype-phenotype information on 32 patients with chromosomal imbalances and ID candidate sequence variants. 2016 artículo científico 2029-4174 https://www.redalyc.org/articulo.oa?id=694073988004 en http://www.redalyc.org/revista.oa?id=6940 Acta medica Lituanica application/pdf Vilniaus Universitetas Acta medica Lituanica (Lituania) Num.2 Vol.23 |
| title | Identification of genetic causes of congenital neurodevelopmental disorders using genome wide molecular technologies |
| topic | Medicina CGH array developmental delay whole exome sequencing Intellectual disability |
| url | https://www.redalyc.org/articulo.oa?id=694073988004 |