Unraveling GRIA1 neurodevelopmental disorders: Lessons learned from the p.(Ala636Thr) variant: Lessons learned from the p.(Ala636Thr) variant
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| Názov: | Unraveling GRIA1 neurodevelopmental disorders: Lessons learned from the p.(Ala636Thr) variant: Lessons learned from the p.(Ala636Thr) variant |
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| Autori: | Nicolai Kohring Tvergaard, Tinatin Tkemaladze, Tommy Stödberg, Malin Kvarnung, Katrina Tatton‐Brown, Diana Baralle, Zeynep Tümer, Allan Bayat |
| Zdroj: | Tvergaard, N K, Tkemaladze, T, Stödberg, T, Kvarnung, M, Tatton-Brown, K, Baralle, D, Tümer, Z & Bayat, A 2024, ' Unraveling GRIA1 neurodevelopmental disorders : Lessons learned from the p.(Ala636Thr) variant ', Clinical Genetics, vol. 106, no. 4, pp. 427-436 . https://doi.org/10.1111/cge.14577 |
| Informácie o vydavateľovi: | Wiley, 2024. |
| Rok vydania: | 2024 |
| Predmety: | Male, Adult, Adolescent, AMPAR, AMPA/genetics, Neurodevelopmental Disorders/genetics, Young Adult, Intellectual Disability, Receptors, GRIA1, Humans, Genetic Predisposition to Disease, Receptors, AMPA, autonomy, Preschool, Child, treatment, developmental trajectory, syndrome, Intellectual Disability/genetics, 3. Good health, Phenotype, natural history, Neurodevelopmental Disorders, Child, Preschool, Mutation, outcome, epilepsy, Female |
| Popis: | Ionotropic glutamate receptors (iGluRs), specifically α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptors (AMPARs), play a crucial role in orchestrating excitatory neurotransmission in the brain. AMPARs are intricate assemblies of subunits encoded by four paralogous genes: GRIA1‐4. Functional studies have established that rare GRIA variants can alter AMPAR currents leading to a loss‐ or gain‐of‐function. Patients affected by rare heterozygous GRIA variants tend to have family specific variants and only few recurrent variants have been reported. We deep‐phenotyped a cohort comprising eight unrelated children and adults, harboring a recurrent and well‐established disease‐causing GRIA1 variant (NM_001114183.1: c.1906G>A, p.(Ala636Thr)). Recurrent symptoms included motor and/or language delay, mild–severe intellectual disability, behavioral and psychiatric comorbidities, hypotonia and epilepsy. We also report challenges in social skills, autonomy, living and work situation, and occupational levels. Furthermore, we compared their clinical manifestations in relation to those documented in patients presenting with rare heterozygous variants at analogous positions within paralogous genes. This study provides unprecedented details on the neurodevelopmental outcomes, cognitive abilities, seizure profiles, and behavioral abnormalities associated with p.(Ala636Thr) refining and broadening the clinical phenotype. |
| Druh dokumentu: | Article |
| Popis súboru: | application/pdf; text |
| Jazyk: | English |
| ISSN: | 1399-0004 0009-9163 |
| DOI: | 10.1111/cge.14577 |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/38890806 https://curis.ku.dk/ws/files/403383251/Clinical_Genetics_2024_Tvergaard_Unraveling_GRIA1_neurodevelopmental_disorders_Lessons_learned_from_the_p_Ala636Thr.pdf https://portal.findresearcher.sdu.dk/da/publications/bfa9574d-6f0a-4941-9d1b-d99c2fd23554 https://doi.org/10.1111/cge.14577 https://publications.scilifelab.se/publication/9fd8622899c54e13b418fc659d75c008 |
| Rights: | CC BY NC ND |
| Prístupové číslo: | edsair.doi.dedup.....a6ee51aa27bede72d5a1dfa55b5fd7f1 |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Ionotropic glutamate receptors (iGluRs), specifically α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptors (AMPARs), play a crucial role in orchestrating excitatory neurotransmission in the brain. AMPARs are intricate assemblies of subunits encoded by four paralogous genes: GRIA1‐4. Functional studies have established that rare GRIA variants can alter AMPAR currents leading to a loss‐ or gain‐of‐function. Patients affected by rare heterozygous GRIA variants tend to have family specific variants and only few recurrent variants have been reported. We deep‐phenotyped a cohort comprising eight unrelated children and adults, harboring a recurrent and well‐established disease‐causing GRIA1 variant (NM_001114183.1: c.1906G>A, p.(Ala636Thr)). Recurrent symptoms included motor and/or language delay, mild–severe intellectual disability, behavioral and psychiatric comorbidities, hypotonia and epilepsy. We also report challenges in social skills, autonomy, living and work situation, and occupational levels. Furthermore, we compared their clinical manifestations in relation to those documented in patients presenting with rare heterozygous variants at analogous positions within paralogous genes. This study provides unprecedented details on the neurodevelopmental outcomes, cognitive abilities, seizure profiles, and behavioral abnormalities associated with p.(Ala636Thr) refining and broadening the clinical phenotype. |
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| ISSN: | 13990004 00099163 |
| DOI: | 10.1111/cge.14577 |