Characterization of an MLC patient carrying two MLC1 variants showing radiological improvement
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of vacuolating leukodystrophy. Approximately 75% of MLC patients have variants in MLC1, while the rest in GLIALCAM, GPRC5B and AQP4. From the GLIALCAM patients, a classical and a benign phenotype can be distinguished, in...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Brain Disorders |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666459323000161 |
| _version_ | 1797637289208184832 |
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| author | Clara Mayayo-Vallverdú Laura Ferigle Marta Vecino-Pérez Julián Lara Virginia Nunes Raúl Estévez |
| author_facet | Clara Mayayo-Vallverdú Laura Ferigle Marta Vecino-Pérez Julián Lara Virginia Nunes Raúl Estévez |
| author_sort | Clara Mayayo-Vallverdú |
| collection | DOAJ |
| description | Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of vacuolating leukodystrophy. Approximately 75% of MLC patients have variants in MLC1, while the rest in GLIALCAM, GPRC5B and AQP4. From the GLIALCAM patients, a classical and a benign phenotype can be distinguished, in which a recessive and dominant inheritance is observed, respectively. Here, we report a new MLC patient harboring two variants in MLC1 with radiological improvement. The patient is heterozygous for the variants c.597+37C>G and c.895–1G>T affecting both mRNA splicing, and the latest causes the deletion p.Pro299_Glu353del. By analyzing mRNA and protein obtained from patient's peripheral blood leukocytes, we could demonstrate the expression of a small amount of wild-type MLC1 mRNA and protein in the patient. Thus, we suggest that the improvement of clinical and radiological abnormalities observed in all remitting MLC patients might be due to the presence of residual amounts of MLC1 protein. |
| first_indexed | 2024-03-11T12:47:13Z |
| format | Article |
| id | doaj.art-ee0bb518887d403fa2a6e96bbe1c4b8d |
| institution | Directory Open Access Journal |
| issn | 2666-4593 |
| language | English |
| last_indexed | 2024-03-11T12:47:13Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Disorders |
| spelling | doaj.art-ee0bb518887d403fa2a6e96bbe1c4b8d2023-11-05T04:05:32ZengElsevierBrain Disorders2666-45932023-09-0111100079Characterization of an MLC patient carrying two MLC1 variants showing radiological improvementClara Mayayo-Vallverdú0Laura Ferigle1Marta Vecino-Pérez2Julián Lara3Virginia Nunes4Raúl Estévez5Genes, Disease and Therapy Program, Molecular Genetics Laboratory-Genes, Disease and Therapy Program-IDIBELL, Genetics Section, Department of Physiological Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, SpainPhysiology Unit, Department of Physiological Sciences, School of Medicine and Health Sciences, Genes, Disease and Therapy Program, Physiology and Pathology of the Functional Relationship Between Glia and Neurons-IDIBELL, Institute of Neurosciences, University of Barcelona, L'Hospitalet de Llobregat 08907, SpainGenes, Disease and Therapy Program, Molecular Genetics Laboratory-Genes, Disease and Therapy Program-IDIBELL, Genetics Section, Department of Physiological Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, SpainHospital Universitario Puerta de Hierro, Madrid, SpainGenes, Disease and Therapy Program, Molecular Genetics Laboratory-Genes, Disease and Therapy Program-IDIBELL, Genetics Section, Department of Physiological Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Corresponding author.Physiology Unit, Department of Physiological Sciences, School of Medicine and Health Sciences, Genes, Disease and Therapy Program, Physiology and Pathology of the Functional Relationship Between Glia and Neurons-IDIBELL, Institute of Neurosciences, University of Barcelona, L'Hospitalet de Llobregat 08907, Spain; Centro de Investigación en red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Corresponding author at: Centro de Investigación en red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of vacuolating leukodystrophy. Approximately 75% of MLC patients have variants in MLC1, while the rest in GLIALCAM, GPRC5B and AQP4. From the GLIALCAM patients, a classical and a benign phenotype can be distinguished, in which a recessive and dominant inheritance is observed, respectively. Here, we report a new MLC patient harboring two variants in MLC1 with radiological improvement. The patient is heterozygous for the variants c.597+37C>G and c.895–1G>T affecting both mRNA splicing, and the latest causes the deletion p.Pro299_Glu353del. By analyzing mRNA and protein obtained from patient's peripheral blood leukocytes, we could demonstrate the expression of a small amount of wild-type MLC1 mRNA and protein in the patient. Thus, we suggest that the improvement of clinical and radiological abnormalities observed in all remitting MLC patients might be due to the presence of residual amounts of MLC1 protein.http://www.sciencedirect.com/science/article/pii/S2666459323000161Megalencephalic leukoencephalopathy with subcortical cystsMyelinReverting phenotypeMutationsMLC1 |
| spellingShingle | Clara Mayayo-Vallverdú Laura Ferigle Marta Vecino-Pérez Julián Lara Virginia Nunes Raúl Estévez Characterization of an MLC patient carrying two MLC1 variants showing radiological improvement Brain Disorders Megalencephalic leukoencephalopathy with subcortical cysts Myelin Reverting phenotype Mutations MLC1 |
| title | Characterization of an MLC patient carrying two MLC1 variants showing radiological improvement |
| title_full | Characterization of an MLC patient carrying two MLC1 variants showing radiological improvement |
| title_fullStr | Characterization of an MLC patient carrying two MLC1 variants showing radiological improvement |
| title_full_unstemmed | Characterization of an MLC patient carrying two MLC1 variants showing radiological improvement |
| title_short | Characterization of an MLC patient carrying two MLC1 variants showing radiological improvement |
| title_sort | characterization of an mlc patient carrying two mlc1 variants showing radiological improvement |
| topic | Megalencephalic leukoencephalopathy with subcortical cysts Myelin Reverting phenotype Mutations MLC1 |
| url | http://www.sciencedirect.com/science/article/pii/S2666459323000161 |
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