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  • Common origin of the Val30Met mutation responsible for the amyloidogenic transthyretin type of familial amyloidotic polyneuropathy

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Common origin of the Val30Met mutation responsible for the amyloidogenic transthyretin type of familial amyloidotic polyneuropathy
  1. H Ohmori1,
  2. Y Ando2,
  3. Y Makita3,
  4. Y Onouchi4,
  5. T Nakajima5,
  6. M J M Saraiva6,
  7. H Terazaki6,
  8. O Suhr7,
  9. G Sobue8,
  10. M Nakamura2,
  11. M Yamaizumi9,
  12. M Munar-Ques10,
  13. I Inoue5,
  14. M Uchino1,
  15. A Hata4,11
  1. 1Department of Neurology, Kumamoto University School of Medicine, Kumamoto, Japan
  2. 2Department of Laboratory Medicine, Kumamoto University School of Medicine, Kumamoto, Japan
  3. 3Department of Pediatrics, Asahikawa Medical College, Asahikawa, Japan
  4. 4Laboratory for Gastrointestinal Diseases, RIKEN SNP Research Center, Yokohama, Japan
  5. 5Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, Japan
  6. 6Instituto de Ciencias Biomedicas, Universidade de Porto, Porto, Portugal
  7. 7Department of Medicine, Umea University Hospital, Umea, Sweden
  8. 8Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan
  9. 9Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan
  10. 10Hospital General Universitario, Murcia, Spain
  11. 11Department of Public Health, Chiba University Graduate School of Medicine, Chiba, Japan
  1. Correspondence to:
 Dr A Hata
 Department of Public Health, Chiba University Graduate School of Medicine, Inohana 1–8-1, Chiba 260–8670, Japan; ahatamed.m.chiba-u.ac.jp

https://doi.org/10.1136/jmg.2003.014803

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    The amyloidogenic transthyretin (TTR) type of familial amyloidotic polyneuropathy (FAP [MIM 176300], http://www.ncbi.nlm.nih.gov/Omim/) is the most common form of hereditary systemic amyloidosis.1–3 It is well known that amyloidogenic TTR resulting from gene mutations is a major constituent of amyloid deposits in tissues of patients with FAP.4 To date, more than 80 mutations of the TTR gene have been associated with human amyloidosis.5 Of those mutations, a mutation changing valine at amino acid 30 to methionine (Val30Met) is the most common,1–3 and only patients with this mutation are found in large foci throughout the world.1,2

    The clinical manifestations of the TTR Val30Met type of FAP in Japan and Portugal are as follows: (1) the disorder is inherited as an autosomal dominant trait with equal sex distribution and high penetrance; (2) the age at onset is late twenties to early forties; (3) polyneuropathy with sensory dissociation starts in the legs and progresses in an ascending fashion; (4) manifestations of various autonomic dysfunctions such as severe orthostatic hypotension, disturbed bowel movement with constipation and diarrhoea, impotence, and urinary incontinence invariably appear during the course of the disease; and (5) amyloid deposition in loco causes dysfunction of various organs.1–3,6 In contrast, the clinical profile of Swedish patients is different: the average age at onset is the middle fifties, and penetrance of the disease is very low. Also, the disease progresses more slowly in Swedish patients than in Japanese and Portuguese patients.7

    The disorder was first described in Portugal in 1952.8 In the 1960s, large foci of patients were found in Japan and Sweden.9,10 In Japan, two large foci of TTR Val30Met type FAP exist: one in Kumamoto prefecture of Kyushu, and the other in Nagano prefecture on the Mainland …

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    Footnotes

    • The authors’ work was supported by grants from the Amyloidosis Research Committee, the Pathogenesis, Therapy of Hereditary Neuropathy Research Committee, the Surveys and Research on Specific Disease, the Ministry of Health and Welfare of Japan, and the Charitable Trust Clinical Pathology Research Foundation of Japan, and Research for the Future Program Grant and Grant-in-Aid for Scientific Research on Priority Areas (C) “Medical Genome Science”, and Grants-in-Aid for Scientific Research (B) 15390275 from the Ministry of Education, Science, Sports and Culture of Japan.

    • Conflict of interest: none declared.