FALS with FUS mutation in Japan, with early onset, rapid progress and basophilic inclusion
| Autor: | Hitoshi Warita, Masashi Aoki, Masaaki Kato, Tetsuya Akiyama, Toshihiro Hokonohara, Naoko Shimakura, Yasuto Itoyama, Hideki Mizuno, Akiko Iwaki, Shinji Togashi, Naoki Suzuki, Hirokazu Furuya, Hidehiko Konno |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Pathology medicine.medical_specialty DNA Mutational Analysis Mutation Missense Biology Inclusion bodies Atrophy Asian People Japan Genetics medicine Humans Age of Onset Amyotrophic lateral sclerosis Family history Genetics (clinical) Family Health Inclusion Bodies Amyotrophic Lateral Sclerosis Exons medicine.disease Penetrance Muscle atrophy Pedigree Basophilic Statistical genetics Disease Progression RNA-Binding Protein FUS Female medicine.symptom |
| Zdroj: | Journal of Human Genetics. 55:252-254 |
| ISSN: | 1435-232X 1434-5161 |
| DOI: | 10.1038/jhg.2010.16 |
| Popis: | Mutations in the fused in sarcoma (FUS, also known as translated in liposarcoma) gene have been recently discovered to be associated with familial amyotrophic lateral sclerosis (FALS) in African, European and American populations. In a Japanese family with FALS, we found the R521C FUS mutation, which has been reported to be found in various ethnic backgrounds. The family history revealed 23 patients with FALS among 46 family members, suggesting a 100% penetrance rate. They developed muscle weakness at an average age of 35.3 years, followed by dysarthria, dysphagia, spasticity and muscle atrophy. The average age of death was 37.2 years. Neuropathological examination of the index case revealed remarkable atrophy of the brainstem tegmentum characterized by cytoplasmic basophilic inclusion bodies in the neurons of the brainstem. We screened 40 FALS families in Japan and found 4 mutations (S513P, K510E, R514S, H517P) in exon 14 and 15 of FUS. Even in Asian races, FALS with FUS mutations may have the common characteristics of early onset, rapid progress and high penetrance rate, although in patients with the S513P mutation it was late-onset. Degeneration in multiple systems and cytoplasmic basophilic inclusion bodies were found in the autopsied cases. |
| Databáze: | OpenAIRE |
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