Actionable Genomics in Clinical Practice: Paradigmatic Case Reports of Clinical and Therapeutic Strategies Based upon Genetic Testing
In clinical settings, the information provided by genetic testing can explain the triggers and processes underlying clinical presentations, such as neurodevelopmental disorders, in up to one third of affected individuals. However, translating this knowledge into better and more personalized clinical...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-02-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/13/2/323 |
| _version_ | 1797479831206625280 |
|---|---|
| author | Merlin G. Butler Daniel Moreno-De-Luca Antonio M. Persico |
| author_facet | Merlin G. Butler Daniel Moreno-De-Luca Antonio M. Persico |
| author_sort | Merlin G. Butler |
| collection | DOAJ |
| description | In clinical settings, the information provided by genetic testing can explain the triggers and processes underlying clinical presentations, such as neurodevelopmental disorders, in up to one third of affected individuals. However, translating this knowledge into better and more personalized clinical management to many appears a distant target. This article presents three paradigmatic cases to exemplify how this translational effort can, at least in some instances, be undertaken today with very positive results: (a) a young girl carrying a chr. 16p11.2 duplication can be screened using targeted exams and undertake therapeutic/preventive interventions related to her genetic diagnosis; (b) a 13-year-old boy with intellectual disability and autism spectrum disorder carries a chr. 11q14.1 deletion, partly spanning the <i>DLG2</i> gene important for synaptic function, and gained over 20 I.Q. points ostensibly due to carbolithium, prescribed in the absence of affective symptoms, exclusively following the pathophysiology pointed out by the genetic results; (c) a 58-year-old woman carries a <i>COL3A1</i> gene variant responsible for the vascular form of Ehler–Danlos syndrome with colon rupture. Detection of this variant in six members of her extended family allows for better clinical management of the proband and targeted genetic counselling for family members at risk of this connective tissue disorder. The unprecedented flow of genetic information available today through new technologies, if interpreted in the light of current knowledge in clinical diagnosis and care of those with connective tissue disorders and neurodevelopmental disturbances, in biology and in neuropsychopharmacology, can promote better clinical and pharmacological treatment, disease surveillance, and management provided and incorporated into the clinical setting. |
| first_indexed | 2024-03-09T21:51:27Z |
| format | Article |
| id | doaj.art-02a5e2ae575744c0898b5e67d53d4771 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T21:51:27Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-02a5e2ae575744c0898b5e67d53d47712023-11-23T20:05:04ZengMDPI AGGenes2073-44252022-02-0113232310.3390/genes13020323Actionable Genomics in Clinical Practice: Paradigmatic Case Reports of Clinical and Therapeutic Strategies Based upon Genetic TestingMerlin G. Butler0Daniel Moreno-De-Luca1Antonio M. Persico2Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, KS 66160, USAGenomic Psychiatry Consultation Service, Verrecchia Clinic for Children with Autism and Developmental Disabilities, Bradley Hospital, East Providence, RI 02915, USADepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, I-41125 Modena, ItalyIn clinical settings, the information provided by genetic testing can explain the triggers and processes underlying clinical presentations, such as neurodevelopmental disorders, in up to one third of affected individuals. However, translating this knowledge into better and more personalized clinical management to many appears a distant target. This article presents three paradigmatic cases to exemplify how this translational effort can, at least in some instances, be undertaken today with very positive results: (a) a young girl carrying a chr. 16p11.2 duplication can be screened using targeted exams and undertake therapeutic/preventive interventions related to her genetic diagnosis; (b) a 13-year-old boy with intellectual disability and autism spectrum disorder carries a chr. 11q14.1 deletion, partly spanning the <i>DLG2</i> gene important for synaptic function, and gained over 20 I.Q. points ostensibly due to carbolithium, prescribed in the absence of affective symptoms, exclusively following the pathophysiology pointed out by the genetic results; (c) a 58-year-old woman carries a <i>COL3A1</i> gene variant responsible for the vascular form of Ehler–Danlos syndrome with colon rupture. Detection of this variant in six members of her extended family allows for better clinical management of the proband and targeted genetic counselling for family members at risk of this connective tissue disorder. The unprecedented flow of genetic information available today through new technologies, if interpreted in the light of current knowledge in clinical diagnosis and care of those with connective tissue disorders and neurodevelopmental disturbances, in biology and in neuropsychopharmacology, can promote better clinical and pharmacological treatment, disease surveillance, and management provided and incorporated into the clinical setting.https://www.mdpi.com/2073-4425/13/2/32316p13.2 duplication<i>COL3A1</i><i>DLG2</i>Ehlers-Danlos syndromelithium |
| spellingShingle | Merlin G. Butler Daniel Moreno-De-Luca Antonio M. Persico Actionable Genomics in Clinical Practice: Paradigmatic Case Reports of Clinical and Therapeutic Strategies Based upon Genetic Testing Genes 16p13.2 duplication <i>COL3A1</i> <i>DLG2</i> Ehlers-Danlos syndrome lithium |
| title | Actionable Genomics in Clinical Practice: Paradigmatic Case Reports of Clinical and Therapeutic Strategies Based upon Genetic Testing |
| title_full | Actionable Genomics in Clinical Practice: Paradigmatic Case Reports of Clinical and Therapeutic Strategies Based upon Genetic Testing |
| title_fullStr | Actionable Genomics in Clinical Practice: Paradigmatic Case Reports of Clinical and Therapeutic Strategies Based upon Genetic Testing |
| title_full_unstemmed | Actionable Genomics in Clinical Practice: Paradigmatic Case Reports of Clinical and Therapeutic Strategies Based upon Genetic Testing |
| title_short | Actionable Genomics in Clinical Practice: Paradigmatic Case Reports of Clinical and Therapeutic Strategies Based upon Genetic Testing |
| title_sort | actionable genomics in clinical practice paradigmatic case reports of clinical and therapeutic strategies based upon genetic testing |
| topic | 16p13.2 duplication <i>COL3A1</i> <i>DLG2</i> Ehlers-Danlos syndrome lithium |
| url | https://www.mdpi.com/2073-4425/13/2/323 |
| work_keys_str_mv | AT merlingbutler actionablegenomicsinclinicalpracticeparadigmaticcasereportsofclinicalandtherapeuticstrategiesbasedupongenetictesting AT danielmorenodeluca actionablegenomicsinclinicalpracticeparadigmaticcasereportsofclinicalandtherapeuticstrategiesbasedupongenetictesting AT antoniompersico actionablegenomicsinclinicalpracticeparadigmaticcasereportsofclinicalandtherapeuticstrategiesbasedupongenetictesting |