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Exp Clin Endocrinol Diabetes 2005; 113(6): 318-323
DOI: 10.1055/s-2005-865646
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

A Heteroplasmic Mitochondrial DNA 3310 Mutation in the ND1 Gene in a Patient with Type 2 Diabetes, Hypertrophic Cardiomyopathy, and Mental Retardation

Y. Hattori1 , 2 , M. Takeoka1 , K. Nakajima2 , T. Ehara3 , M. Koyama4
  • 1Department of Molecular Oncology, Division of Molecular and Cellular Biology Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto, Japan
  • 2Department of Internal Medicine, Asama General Hospital, Saku, Japan
  • 3Department of Histopathology, Shinshu University School of Medicine, Matsumoto, Japan
  • 4Department of Pathology, Komoro Kosei General Hospital, Komoro, Japan
Further Information

Publication History

Received: July 10, 2004 First decision: September 20, 2004

Accepted: March 17, 2005

Publication Date:
23 June 2005 (online)

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Abstract

A mentally retarded 57-year-old Japanese man with maternally-inherited type 2 diabetes was found to have hypertrophic cardiomyopathy (HCM) that was associated with pathological changes in the myocardial mitochondria. The mitochondrial DNA (mtDNA) of this patient was examined and a C3310 T mutation was found in the ND1 gene, which resulted in the substitution of serine for proline. The normal 3310 mtDNA band could not be detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in mtDNA from his myocardium, pancreas, cerebral tissue, skeletal muscle, and lymphocytes. However two clones sequenced from his pancreatic tissue did not show this C3310 T mutation while forty-eight did. Mitochondria isolated from the lymphocytes of his two sisters also had this mutation. mtDNA point mutations in the ND1 gene region reported thus far have been mostly homoplasmic. However, the C3310 T point mutation that was found in this patient was heteroplasmic, which is a high level of mutation and may represent the pathogenic gene that was responsible for causing mitochondrial disease.

Key words

Type 2 diabetes - hypertrophic cardiomyopathy - left ventricular hypertrophy - ND1 gene - heteroplasmic mutation

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Y. Hattori

Department of Molecular Oncology
Division of Molecular and Cellular Biology Institute on Aging and Adaptation
Shinshu University Graduate School of Medicine

Asahi 3-1-1

Matsumoto

Japan

Phone: + 81263372723

Fax: + 81 2 63 37 27 24

Email: u-chan@avis.ne.jp

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