Abstract
ABSTRACTThe objective of this study was to describe the clinical characteristics of syndromic neonatal diabetes in a family with a GATA6 mutation. A girl, currently aged 12 years 3 months, was born with intrauterine growth retardation: weight 1600 g (–4.3 SDS) at term. After birth, foramen ovale and patent ductus arteriosus (PDA) were diagnosed by echocardiography. Diabetes was diagnosed on the 9th day after birth. Exocrine pancreatic insufficiency was clinically diagnosed at about 2 years of age and pancreatic agenesis was revealed later by magnetic resonance imaging. Her father had undergone surgery during infancy for PDA and had developed insulin dependent diabetes at 12 years of age. Ultrasound revealed a thin pancreas with normal length and anatomical structure. He has subclinical exocrine pancreatic insufficiency, low insulin needs and no late complications of diabetes up to the age of 40 years. Sequencing of GATA6 identified a heterozygous splicing mutation, 1136-2A>G, in the girl and her father. Testing of the paternal grandparents showed that the mutation was likely to have arisen de novo in the father. Identification of a GATA6 mutation explains the cardiac anomalies and diabetes in this family. This case highlights the marked intra-familial variability of both exocrine and endocrine pancreatic phenotypes in patients with GATA6 mutations.
Highlights
Genome sequencing technologies have helped to establish the etiology of diabetes mellitus (DM) in a small group of pediatric patients presenting non-autoimmune mechanisms of impaired insulin secretion
In this report we describe the clinical characteristics of syndromic neonatal diabetes in a family, father and daughter, with a GATA6 mutation
The father was born with normal birth weight. He underwent a cardiac operation in infancy for patent ductus arteriosus (PDA) and developed diabetes at the age of 12 years
Summary
Genome sequencing technologies have helped to establish the etiology of diabetes mellitus (DM) in a small group of pediatric patients presenting non-autoimmune mechanisms of impaired insulin secretion. More than 20 gene mutations causing permanent (PNDM) or transient (TNDM) neonatal diabetes mellitus have been identified [1]. The transcription factor GATA6 has been intensively studied after the discovery of its role in the development of the pancreas. GATA 4/5/6 subfamily presents primary endodermal and mesodermal transcription factors, expressed in the primitive endoderm and extra-embryonic tissues for supporting the growing epiblast [2,3,4] and endodermal differentiation [5]. GATA4/5/6 ensure the anatomical and functional development of the pancreas, heart, blood vessels, hepatobiliary system, urogenital tract, thyroid gland as well as the brain [6,7]. GATA 4/6 have a leading role in the transcriptional network hierarchy in pancreatic multipotent progenitors arisen from the foregut endoderm [8,9]
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