Clinical and Genetic Investigation of a Japanese Family With Cardiac Fabry Disease Identification of a Novel <i>α</i>-Galactosidase A Missense Mutation (G195V)

Naoki Nakagawa; Hiroki Maruyama; Takayuki Ishihara; Utako Seino; Jun-ichi Kawabe; Fumihiko Takahashi; Motoi Kobayashi; Atsushi Yamauchi; Yukie Sasaki; Naka Sakamoto; Hisanobu Ota; Yasuko Tanabe; Toshiharu Takeuchi; Toshihiro Takenaka; Kenjiro Kikuchi; Naoyuki Hasebe

doi:10.1536/ihj.52.308

Clinical Studies

Clinical and Genetic Investigation of a Japanese Family With Cardiac Fabry Disease

Identification of a Novel α-Galactosidase A Missense Mutation (G195V)

Naoki Nakagawa, Hiroki Maruyama, Takayuki Ishihara, Utako Seino, Jun-ichi Kawabe, Fumihiko Takahashi, Motoi Kobayashi, Atsushi Yamauchi, Yukie Sasaki, Naka Sakamoto, Hisanobu Ota, Yasuko Tanabe, Toshiharu Takeuchi, Toshihiro Takenaka, Kenjiro Kikuchi, Naoyuki Hasebe

Author information

Naoki Nakagawa
Division of Cardiology, Nephrology, Pulmonology and Neurology, Department of Internal Medicine, Asahikawa Medical University
Hiroki Maruyama
Department of Clinical Nephroscience, Niigata University Graduate School of Medical and Dental Sciences
Takayuki Ishihara
Department of Clinical Nephroscience, Niigata University Graduate School of Medical and Dental Sciences
Utako Seino
Department of Clinical Nephroscience, Niigata University Graduate School of Medical and Dental Sciences
Jun-ichi Kawabe
Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University
Fumihiko Takahashi
Department of Internal Medicine, Hokkaido Prefectural Haboro Hospital
Motoi Kobayashi
Division of Cardiology, Nephrology, Pulmonology and Neurology, Department of Internal Medicine, Asahikawa Medical University
Atsushi Yamauchi
Division of Cardiology, Nephrology, Pulmonology and Neurology, Department of Internal Medicine, Asahikawa Medical University
Yukie Sasaki
Division of Cardiology, Nephrology, Pulmonology and Neurology, Department of Internal Medicine, Asahikawa Medical University
Naka Sakamoto
Division of Cardiology, Nephrology, Pulmonology and Neurology, Department of Internal Medicine, Asahikawa Medical University
Hisanobu Ota
Division of Cardiology, Nephrology, Pulmonology and Neurology, Department of Internal Medicine, Asahikawa Medical University
Yasuko Tanabe
Division of Cardiology, Nephrology, Pulmonology and Neurology, Department of Internal Medicine, Asahikawa Medical University
Toshiharu Takeuchi
Division of Cardiology, Nephrology, Pulmonology and Neurology, Department of Internal Medicine, Asahikawa Medical University
Toshihiro Takenaka
Division of Cardiac Repair and Regeneration, Graduate School of Medical and Dental Sciences, Kagoshima University
Kenjiro Kikuchi
Division of Cardiology, Nephrology, Pulmonology and Neurology, Department of Internal Medicine, Asahikawa Medical University
Naoyuki Hasebe
Division of Cardiology, Nephrology, Pulmonology and Neurology, Department of Internal Medicine, Asahikawa Medical University

Keywords: Left ventricular hypertrophy, Hereditary cardiovascular diseases, Glycosphingolipid deposition

JOURNAL FREE ACCESS

2011 Volume 52 Issue 5 Pages 308-311

DOI https://doi.org/10.1536/ihj.52.308

Details

Abstract

Fabry disease is an X-linked lysosomal storage disorder caused by mutations of the α-galactosidase A gene (GLA), and the disease is a relatively prevalent cause of left ventricular hypertrophy mimicking idiopathic hypertrophic cardiomyopathy. We assessed clinically 5 patients of a three-generation family and also searched for GLA mutations in 10 family members. The proband had left ventricular hypertrophy with localized thinning in the basal posterior wall and late gadolinium enhancement (LGE) in the near-circumferential wall in cardiovascular magnetic resonance images and her sister had vasospastic angina pectoris without organic stenosis of the coronary arteries. LGE notably appeared in parallel with decreased α-galactosidase A activity and increased NT-pro BNP in our patients. We detected a new GLA missense mutation (G195V) in exon 4, resulting in a glycine-to-valine substitution. Of the 10 family members, 5 family members each were positive and negative for this mutation. These new data extend our clinical and molecular knowledge of GLA gene mutations and confirm that a novel missense mutation in the GLA gene is important not only for a precise diagnosis of heterozygous status, but also for confirming relatives who are negative for this mutation.

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