Pancreatic Agenesis due to Compound Heterozygosity for a Novel Enhancer and Truncating Mutation in the PTF1A Gene
Journal Title: Journal of Clinical Research in Pediatric Endocrinology - Year 2017, Vol 9, Issue 3
Abstract
Neonatal diabetes, defined as the onset of diabetes within the first six months of life, is very rarely caused by pancreatic agenesis. Homozygous truncating mutations in the PTF1A gene, which encodes a transcriptional factor, have been reported in patients with pancreatic and cerebellar agenesis, whilst mutations located in a distal pancreatic-specific enhancer cause isolated pancreatic agenesis. We report an infant, born to healthy non-consanguineous parents, with neonatal diabetes due to pancreatic agenesis. Initial genetic investigation included sequencing of KCNJ11, ABCC8 and INS genes, but no mutations were found. Following this, 22 neonatal diabetes associated genes were analyzed by a next generation sequencing assay. We found compound heterozygous mutations in the PTF1A gene: A frameshift mutation in exon 1 (c.437_462 del, p.Ala146Glyfs*116) and a mutation affecting a highly conserved nucleotide within the distal pancreatic enhancer (g.23508442A>G). Both mutations were confirmed by Sanger sequencing. Isolated pancreatic agenesis resulting from compound heterozygosity for truncating and enhancer mutations in the PTF1A gene has not been previously reported. This report broadens the spectrum of mutations causing pancreatic agenesis.
Authors and Affiliations
Monica Gabbay, Sian Ellard, Elisa De Franco, Regina S. Moisés
Keywords
Related Articles
- EP ID EP223895
- DOI 10.4274/jcrpe.4494
- Views 201
- Downloads 0
A Novel Variant c.97C>T of the Growth Hormone Releasing Hormone Receptor Gene Causes Isolated Growth Hormone Deficiency Type Ib
Congenital isolated growth hormone deficiency (IGHD) type 1b is an autosomal recessive genetic condition caused by mutations of growth hormone (GH)-1 or the growth hormone releasing hormone receptor (GHRH-R) genes. Affec...
Management of Thyrotoxicosis in Children and Adolescents: A Turkish Multi-center Experience
Objective: To determine the demographic and biochemical features of childhood and juvenile thyrotoxicosis and treatment outcome. Methods: We reviewed the records of children from 22 centers in Turkey who were diagnosed w...
Effect of Intrahepatic Cholestasis of Pregnancy on Neonatal Birth Weight: A Meta-Analysis
Objective: To evaluate the effect of intrahepatic cholestasis of pregnancy (ICP) on neonatal birth weight. Methods: Potential articles were identified by searching PubMed and Web of Science databases on April 30th, 2017....
Transient Neonatal Diabetes due to a Mutation in KCNJ11 in a Child with Klinefelter Syndrome
Klinefelter syndrome is the most frequent chromosomal aneuploidy in males occurring in about 1 in 660 males. Epidemiological studies have demonstrated increased risk of type 1 diabetes and type 2 diabetes in adults with...
Follow-up Findings in a Turkish Girl with Pseudohypoparathyroidism Type Ia Caused by a Novel Heterozygous Mutation in the GNAS Gene
Pseudohypoparathyroidism type Ia (PHP-Ia) is characterized by multihormone resistance and an Albright hereditary osteodystrophy (AHO) phenotype. It is caused by heterozygous mutations in GNAS gene. Clinical and biochemic...