Pancreatic Agenesis due to Compound Heterozygosity for a Novel Enhancer and Truncating Mutation in the PTF1A Gene

Pancreatic Agenesis due to Compound Heterozygosity for a Novel Enhancer and Truncating Mutation in the PTF1A Gene

Author Gabbay, Monica Autor UNIFESP Google Scholar
Ellard, Sian Google Scholar
De Franco, Elisa Google Scholar
Moises, Regina S. Autor UNIFESP Google Scholar
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.
Keywords Pancreatic agenesis
neonatal diabetes
PTF1A gene
Language English
Date 2017
Published in Journal Of Clinical Research In Pediatric Endocrinology. Findikzade, v. 9, n. 3, p. 274-277, 2017.
ISSN 1308-5727 (Sherpa/Romeo, impact factor)
Publisher Galenos Yayincilik
Extent 274-277
Origin http://dx.doi.org/10.4274/jcrpe.4494
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000410406300013
URI http://repositorio.unifesp.br/handle/11600/51316

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