1. The first de novo mutation in the neuroserpin gene.
- Author
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Godfraind, Catherine, Coutelier, Marie, Andries, Sibille, Van Rijckevorsel, Germaine, Scaravilli, Francesco, and Vikkula, Miikka
- Subjects
GENETIC mutation ,GENES ,PROTEASE inhibitors ,DEMENTIA ,MYOCLONUS ,TREMOR ,NEUROLOGICAL disorders ,PROTEINS - Abstract
Point mutations in the gene referred as neuroserpin or PI12 (protease inhibitor 12), located at 3q26, have recently been associated to 5 familial cases of autosomal dominant presenile dementia named Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB: OMIM #604218). Severity of clinical course is linked to the site of point mutation. Exon 2 PI12 mutations have been associated to later clinical onset than exon 9. Clinical spectrum includes progressive cognitive decline, myoclonus, seizure, tremor, dysarthria and chorea. Neuropathology is characterized by intra-cytoplasmic neuronal inclusions of polymerized mutant protein called Collin's body. These inclusions are strongly periodic acid-Schiff (PAS) positive and diastase resistant, similar to ones observed in the liver in alpha-1-antitrypsin deficiency. We report a female patient, who at 8-years of age developed aggressive behaviour, intellectual decline and intractable epilepsy, for which she underwent neurosurgical sub-pial transections. A brain biopsy was performed and showed classical histological aspects of FENIB. PI12 sequencing revealed a novel exon 9 mutation. Paternity test was in concordance with a de novo mutation. This is the youngest reported patient affected by FENIB, and the first proof of non-familial occurrence of this genetic dementia. [ABSTRACT FROM AUTHOR]
- Published
- 2007