Am J Med Genet A. 2019 Jul 12. doi: 10.1002/ajmg.a.61294. [Epub ahead of print]
GATA6 mutations: Characterization of two novel patients and a comprehensive overview of the GATA6 genotypic and phenotypic spectrum.
Škorić-Milosavljević D1, Tjong FVY1, Barc J1, Backx APCM2, Clur SB2, van Spaendonck-Zwarts K3, Oostra RJ4, Lahrouchi N1, Beekman L1, Bökenkamp R5, Barge-Schaapveld DQCM6, Mulder BJ1, Lodder EM1, Bezzina CR1, Postma AV3,4.
Author information
The first human mutations in GATA6 were described in a cohort of patients with persistent truncus arteriosus, and the phenotypic spectrum has expanded since then. This study underscores the broad phenotypic spectrum by presenting two patients with de novo GATA6 mutations, both exhibiting complex cardiac defects, pancreatic, and other abnormalities. Furthermore, we provided a detailed overview of all published human genetic variation in/near GATA6 published to date and the associated phenotypes (n = 7. We conclude that the most common phenotypes associated with a mutation in GATA6 were structural cardiac and pancreatic abnormalities, with a penetrance of 87 and 60%, respectively. Other common malformations were gallbladder agenesis, congenital diaphragmatic hernia, and neurocognitive abnormalities, mostly developmental delay. Fifty-eight percent of the mutations were de novo, and these patients more often had an anomaly of intracardiac connections, an anomaly of the great arteries, and hypothyroidism, compared with those with inherited mutations. Functional studies mostly support loss-of-function as the pathophysiological mechanism. In conclusion, GATA6 mutations give a wide range of phenotypic defects, most frequently malformations of the heart and pancreas. This highlights the importance of detailed clinical evaluation of identified carriers to evaluate their full phenotypic spectrum.

© 2019 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc.

GATA6; congenital heart disease; heart; mutation; pancreas; phenotypic spectrum

PMID: 31301121 DOI: 10.1002/ajmg.a.61294