The PTF1A gene encodes a component of the Pancreatic Transcription Factor 1 (PTF1) complex. This transcription factor plays a role in cell-fate determination in various organs. Specifically, the protein is responsible for determining whether cells allocated to the pancreatic buds continue towards pancreatic organogenesis or revert to duodenal fates. Other biological processes regulated by PTF1A include amacrine cell differentiation, cerebellum development, neuron fate commitment and retina layer formation.
The gene has been implicated in Pancreatic Agenesis 2 (PAGEN2), a condition found in association with Permanent Neonatal Diabetes Mellitus (PNDM). It has also been implicated in Pancreatic and Cerebellar Agenesis (PACA), a disorder characterized by neurological, skeletal, respiratory and cardiovascular defects, along with PNDM and pancreatic agenesis.
The PTF1A gene is located on the short arm of chromosome 10 and spans a length of 1.9 kb of DNA. Its coding sequence is contained within just 2 exons and it encodes a 34.9 kDa protein product consisting of 328 amino acids. The gene is expressed in the pancreas. PTF1A mutations implicated in disease include mainly nonsense variants that result in premature truncation of the protein. A 24 bp deletion in the gene (c. 437_460del), predicted to remove the C-terminal domain, has been associated with PACA in a Saudi child.
Deeb et al. (2016) analyzed Neonatal Diabetes Mellitus (NDM) patients and characterized their genetic and clinical features. The authors found 25 cases of NDM in Abu Dhabi between the years 1985-2013, giving an incidence rate of 1:29,241 live births. Of these, 23 were Permanent Neonatal Diabetes Mellitus (PNDM) cases and 2 patients had Transient Neonatal Diabetes Mellitus (TNDM). Genetic analysis of this cohort revealed the deletion of the PTF1A enhancer in two first cousins. Both patients presented with NDM in infancy and pancreatic agenesis on MRI. They required daily insulin administration.