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A novel GATA4 mutation completely segregated with atrial septal defect in a large Japanese family
  1. A Okubo1,2,
  2. O Miyoshi1,3,
  3. K Baba4,
  4. M Takagi5,
  5. K Tsukamoto2,
  6. A Kinoshita1,6,
  7. K Yoshiura1,6,
  8. T Kishino6,7,
  9. T Ohta6,7,
  10. N Niikawa1,6,
  11. N Matsumoto1,6,8
  1. 1Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  2. 2Department of Clinical Pharmacy, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  3. 3Department of Psychiatry, Mie University School of Medicine, Tsu, Japan
  4. 4Baba Clinic, Nagasaki, Japan
  5. 5Joseph Clinic, Nagasaki, Japan
  6. 6CREST, Japan Science and Technology Agency, Kawaguchi, Japan
  7. 7Division of Functional Genomics, Center for Frontier Life Sciences, Nagasaki University, Nagasaki, Japan
  8. 8Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  1. Correspondence to:
 Dr N Matsumoto
 Department of Human Genetics, Yokohama City University Graduate School of Medicine, Fukuura 3–9, Kanazawa-ku, Yokohama 236–0004, Japan;

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Atrial septal defect (ASD) is characterised by left-to-right shunting and increased right ventricular output.1 Approximately 5–10% of congenital heart diseases (CHD) are due to ASD which is one of the most frequent CHD found in human adults.2 ASD has been presumed to be caused by genetic factors.3,4 Recently, a few genes have been implicated in syndromic and non-syndromic ASD. Mutations in T-BOX5 at 12q24.1,5,6NKX2.5 at 5q34,7,8EVC at 4p16.1,9 and GATA4 at 8p23.1–p2210 cause Holt-Oram syndrome with ASD or ventricular septal defect (VSD), non-syndromic CHD including ASD and atrioventricular conduction abnormalities, Ellis-van Creveld syndrome with ASD, and a familial isolated ASD, respectively.

We encountered a large family of four generations where 11 members were affected with ASD, and where disease transmission was consistent with an autosomal dominant mode of inheritance. Here we report a novel mutation of GATA4 in this family.



A large Japanese family composed of a total of 29 members across four generations contained 11 members with ASD (I-1, II-2, II-6, II-7, III-1, III-2, III-4, IV-1, IV-2, IV-5, and IV-6; fig 1A). ASD in five patients (II-7, III-1, III-2, IV-1, and IV-2) was surgically repaired, and two patients (II-2 and IV-1) also had pulmonary stenosis (PS). The heart defects in eight subjects (II-2, II-7, III-1, III-2, IV-1, and IV-2) including two diseased subjects (I-1 and II-6) had been clinically diagnosed by one of co-authors (BK) on the basis of their past histories, operation records, 12-lead electrocardiograms, and echocardiograms with colour Doppler apparatus (fig 1A), while those in three other subjects …

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  • Conflict of interest: none declared.