Abstract 113: Fibro Calculous Pancreatic Diabetes (FCPD): Panel of genetic mutations

Background: Exact etiology forFibro Calculous Pancreatic Diabetes (FCPD) is not well understood, hypothesised to be a multifactorial, with role of both genetic and environmental components. Few genetic mutations have been postulated to be associated with FCPD in previous studies, serine protease inhibitor Kazal type 1 gene (SPINK1) being the most common. Association of Cationic trypsinogen (PRSS1), Anionic trypsinogen (PRSS2), Chymotrypsinogen C (CTRC), Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations too have been observed, though the data is very scarce & conflicting. We are not aware of a single study which has comprehensively looked into various mutations together. Objectives: To look for panel of known genetic mutations (SPINK, PRSS1, PRSS2, CTRC & CFTR) in FCPD patients Methods: This cross-sectional study was carried out from July 2021 to October 2022. Patients attending Endocrine OPD who fulfilled the Mohan et al criteria for FCPD were recruited for the study. DNA was isolated from whole blood using commercially available kits. Quantification and purity of the isolated DNA was determined in duplicate by measuring absorbance at 260 nm and 280 nm using a Bio Spectrometer. The allele-specific PCR and nested PCRwas performed followed by Agarose gel electrophoresis and Sanger sequencing method confirmed mutation positive sample. Results: Overall 13/30 (43%) patients have been detected positive for known mutations. Maximum mutations were found in SPINK gene. While 8/30 (27%) patients were SPINK mutation positive, 4/30 (13%) patients were PRSS mutation positive and one patient was positive for CTRC mutation. No mutation was detected in CFTR gene in these 30 patients. Among SPINK gene mutations, SPINK N34S mutation is the most common, detected in 6 (20%) patients. SPINK 1 IVS1-37T>C and SPINK1 P55S mutations were detected in 2 patients each & SPINK 1 IVS3+2T>C was detected 01 patient. Those two patients who were positive for SPINK1 P55S had SPINK N34S mutation as well. Similarly one out of the two patients positive for SPINK 1 IVS1-37T>C mutation, also had SPINK N34S mutation. Only patient who had SPINK 1 IVS3+2T>C mutation positivity, was also positive for SPINK N34 S & PRSS1N29I. Among PRSS1 gene mutations, PRSS1N29I is the most common, detected in 04 patients. One patient has PRSS1 R122H mutation positivity; however, that patient was also positive for PRSS1N29I gene mutation. Only one patient was positive for CTRC gene in CTRC EXON 2-3. No mutation wasdetected in CTRC promoter region & other Exons. Conclusion: In our study of 30 FCPD patients, 43% patients are associated with various known genetic mutations. SPINK mutations are most common (27%) with SPINK N34S being most common (20%). PRSS mutations are the second most common mutations, seen in 13% patients with PRSS1N29I being present in all such cases.