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The first de novo mutation in the neuroserpin gene
Author(s) -
Godfraind Catherine,
Coutelier Marie,
Andries Sibille,
Rijckevorsel Germaine,
Scaravilli Francesco,
Vikkula Miikka
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a30
Subject(s) - exon , neuropathology , myoclonus , mutation , point mutation , pathology , dementia , genetics , frontotemporal dementia , medicine , biology , gene , neuroscience , disease
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.