Studies link genetic mutations to language impairment, ADHD, and myasthenia gravis

P512L Positive for proteins associated with NDs. EGFP-CAPRIN1 . aggregates are considered P512L Positive for SCNA. b aggregates of EGFP-CAPRIN1 P512L Positive for ATXN2. cEGFP-CAPRIN1 P512L Positive totals for GEMIN5. dEGFP-CAPRIN1 P512L Positive aggregates for SNRNP200. (Scale bar: 10 µm). credit: Cellular and Molecular Life Sciences (2022). DOI: 10.1007/s00018-022-04544-3″ width=”800″ height=”530″/>

Caprin 1P512L Aggregates are positive for proteins associated with NDs. A EGFP-CAPRIN1P512L Totals are positive for SCNA. b EGFP-CAPRIN1P512L The sums are positive for ATXN2. c EGFP-CAPRIN1P512L The aggregates are positive for GEMIN5. D-EGFP-CAPRIN1P512L Aggregates are positive for SNRNP200. (Scale bar: 10 µm). attributed to him: Cellular and Molecular Life Sciences (2022). DOI: 10.1007/s00018-022-04544-3

Two studies have revealed that specific disorders of the CAPRIN1 gene have serious consequences for people. First, the research team showed that insufficient production of the protein CAPRIN1 in the brain can lead to disabilities, including autism spectrum disorders, attention deficit hyperactivity disorder (ADHD), and language disorders.

Furthermore, scientists have identified a specific mutation in the CAPRIN1 gene (CAPRIN1P512L) that leads to an abnormal buildup of proteins, causing an unsteady gait and muscle weakness (myasthenia gravis). Both studies have been published in journals brain And the Cellular and Molecular Life Sciences.

These new ideas are made possible by exome analyses, in which scientists observe which genes have been altered in a cell. The team also used the GeneMatcher database – a platform where researchers and clinicians share information about mutations in genes and associated diseases.

The research team identified twelve patients who had mutations in the CAPRIN1 gene. In them, only half the amount of protein was produced. Lisa Pavinato, a doctoral researcher on Prof. Alfredo Brusco’s team at the University of Turin and a DAAD fellow with Prof. Dr. Brunhild Wirth at the University of Cologne, has discovered a link between a lack of protein production and some neurological diseases. weakness.

All affected subjects had speech disorders, 82 percent had ADHD, and 67 percent were affected by it. Autism spectrum disorders and other neurodevelopmental disorders. The function of CAPRIN1 was confirmed in laboratory experiments with human induced pluripotent stem cells in which the CAPRIN1 gene was turned off using CRISPR/Cas9 technology, creating the conditions experienced by the affected individuals.

Cells with the CAPRIN1 mutation develop shortened processes and defective circuits that show reduced electrical activity Compared to healthy neurons without the mutation. In contrast, control neurons without the CAPRIN1 mutation form long processes, and develop into complex networks.

Furthermore, the team also detected changes in translation, one of the most important cellular processes for cell formation and error-free function. In fact, due to mistranslation, the mutant neurons began to deteriorate and form clumps after a few days. The results of this research were published in the article “Individual deficiency in CAPRIN1 leads to a neurodevelopmental disorder with language impairment, ADHD and autism spectrum disorder” in brain.

In the second study, GeneMatcher was used to identify three children from different families with a newly developed point mutation at a specific locus of the CAPRIN1 gene: the exchange of the amino acid proline to leucine at position 512.

The three children show the same symptoms of early movement disorders (ataxia), impaired speech motor skills (dysarthria), memory disorders, and myasthenia gravis. Andrea Dele-Vedov, a doctoral researcher in Professor Wirth’s team, showed that this specific mutation leads to numerous protein clumps in neurons similar to other neurodegenerative diseases such as Parkinson’s, Alzheimer’s or ataxia. In addition, the activity of neurons was reduced.

The study “CAPRIN1P512L that causes abnormal protein accumulation and is associated with early ataxia” appeared in Cellular and Molecular Life Sciences.

The new research findings are important not only for affected patients and their families, who spend years searching for answers to understand the cause of their disease, but also for clinicians, who can now make faster and more accurate diagnoses. Dr.. Brunhild Wirth, Director of the Institute of Human Genetics at the University Hospital Cologne, who led the studies with national and international teams.


The first mouse model with the tRNALeu mutation was developed in the mitochondria


more information:
Lisa Pavinato et al., single deficiency of CAPRIN1 leads to a neurodevelopmental disorder with language impairment, ADHD and autism spectrum disorder, brain (2022). DOI: 10.1093/brain/awac278

Andrea Delle Vedove et al, CAPRIN1P512L causes aberrant protein accumulation and is associated with early ataxia, Cellular and Molecular Life Sciences (2022). DOI: 10.1007/s00018-022-04544-3

Introduction of
University of Cologne


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