Familial GATA6 mutation causing variably expressed diabetes mellitus and cardiac and renal abnormalities

[摘要] A 26-year-old man presented with a combination of permanent neonatal diabetes due to pancreatic aplasia, complexcongenital heart disease, central hypogonadism and growth hormone deficiency, structural renal abnormalities withproteinuria, umbilical hernia, neurocognitive impairment and dysmorphic features. His older brother had diabetesmellitus due to pancreatic hypoplasia, complex congenital heart disease, hypospadias and umbilical hernia. Their fatherhad an atrial septal defect, umbilical hernia and diabetes mellitus diagnosed incidentally in adulthood on employmentscreening. The proband’s paternal grandmother had a congenital heart defect. Genetic testing of the proband revealeda novel heterozygous missense variant (Chr18:g.19761441T>C, c.1330T>C, p.Cys444Arg) in exon 4 of GATA6, which isclass 5 (pathogenic) using American College of Medical Genetics and Genomics guidelines and is likely to account for hismultisystem disorder. The same variant was detected in his brother and father, but not his paternal grandmother. Thisnovel variant of GATA6 likely occurred de novo in the father with autosomal dominant inheritance in the proband andhis brother. The case is exceptional as very few families with monogenic diabetes due to GATA6 mutations have beenreported to date and we describe a new link between GATA6 and renal pathology.

[学科分类] 血液学