Clinical and genetic investigation of a Japanese family with cardiac fabry disease. Identification of a novel α-galactosidase A missense mutation (G195V).
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.
Division of Cardiology, Nephrology, Pulmonology and Neurology, Department of Internal Medicine, Asahikawa Medical University, Hokkaido, Japan.
Naoki
N
Nakagawa
Hiroki
H
Maruyama
Takayuki
T
Ishihara
Utako
U
Seino
Jun-ichi
J
Kawabe
Fumihiko
F
Takahashi
Motoi
M
Kobayashi
Atsushi
A
Yamauchi
Yukie
Y
Sasaki
Naka
N
Sakamoto
Hisanobu
H
Ota
Yasuko
Y
Tanabe
Toshiharu
T
Takeuchi
Toshihiro
T
Takenaka
Kenjiro
K
Kikuchi
Naoyuki
N
Hasebe
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D002037:Bundle-Branch Block / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D017023:Coronary Angiography; D003329:Coronary Vasospasm / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D004452:Echocardiography; D004562:Electrocardiography; D005091:Exons / Q000235:genetics; D000795:Fabry Disease / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D009206:Myocardium / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010375:Pedigree; D010446:Peptide Fragments / Q000097:blood; D012815:Signal Processing, Computer-Assisted; D014633:Valine / Q000235:genetics; D055815:Young Adult; D000519:alpha-Galactosidase / Q000235:genetics*
D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000519:alpha-Galactosidase; D014633:Valine; D005998:Glycine