[Clinical and genetic characteristics of fibrocalculous pancreatic diabetes associated with SPINK1 gene mutations in a patient with type 1 diabetes]

Abstract

To investigate the pathogenic mechanisms of a patient with type 1 diabetes mellitus (T1DM) complicated with fibrocalculous pancreatic diabetes at Tianjin Medical University General Hospital Airport Site in June 2024, clinical and genetic characteristic analyses were performed. Potential pathogenic genes were screened by whole-exome sequencing (WES), and Sanger sequencing validated the identified genetic variants within the family. The proband exhibited elevated blood glucose levels and positivity for tyrosine phosphatase antibodies, suggesting a diagnosis of T1DM. Multiple calcifications in the pancreas were observed in the proband. Genetic testing revealed that the proband carried two variants in the serine peptidase inhibitor Kazal type 1 (SPINK1) gene, namely, c.194+2T>C and c.-215G>A. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the c.194+2T>C mutation is preliminarily classified as pathogenic, while the c.-215G>A variant is classified as a variant of uncertain significance (VUS). Bioinformatics analysis indicated that the c.194+2T>C variant in the SPINK1 gene results in a truncated protein, affecting the three-dimensional structure and activity of the protein. This mutation is in complete linkage disequilibrium with the c.-215G>A variant, which may have a protective function and influence the clinical phenotype. Given that the patient also has T1DM and FCPD, there should be increased awareness of the co-occurrence of both types of diabetes to prevent misdiagnosis and underdiagnosis.