PDX1-MODY: A rare missense mutation as a cause of monogenic diabetes

• Published in: European journal of medical genetics 2021-05, Vol.64 (5), p.104194-104194, Article 104194
• Main Authors: Abreu, Gabriella de M., Tarantino, Roberta M., da Fonseca, Ana Carolina P., de Souza, Ritiele B., Soares, Camila A.P.D., Cabello, Pedro H., Rodacki, Melanie, Zajdenverg, Lenita, Zembrzuski, Verônica M., Campos Junior, Mário
• Format: Article
• Language: English
• Subjects: Diabetes mellitus; MODY; MODY4; Monogenic diabetes; Mutation; PDX1
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2021.104194

Maturity-Onset Diabetes of the Young type 4 is a rare form of diabetes mellitus, caused by mutations in the PDX1 gene. However, only a few mutations in this gene have been associated as a cause of monogenic diabetes up to date. It makes difficult to create a clinical manifestation profile of this disease and, consequently, to improve the therapeutic management for these patients. Here we report a normal weight woman, diagnosed with diabetes mellitus at 27 years old, during her first pregnancy. At the time of the recruitment, she was 40 years old and had a body mass index of 23.9 kg/m2, glycated hemoglobin level of 9.6%, and fasting plasma glucose (FPG) of 254 mg/dL. She presented no diabetic complications and she was being treated with insulin. She reported a family history of diabetes mellitus characteristic of an autosomal dominant mode of inheritance. Molecular analysis of the PDX1 gene revealed the missense variant c.532G > A (p.(Glu178Lys)) segregating from the patient to her son, reported as diabetic. It was absent in her healthy daughter. The c.532G > A seems to be a rare variant, absent in human variants databases, and among 86 normoglycemic controls. Eight in silico algorithms classified this variant as probably pathogenic. Additionally, analysis of the evolutionary conservation showed the glutamic acid in the position 178 of PDX-1 protein as conserved among several species. Our findings reinforce the importance of screening rare MODY genes among families with suspicion of monogenic diabetes to help better understand the clinical manifestations of this disease. •PDX1-MODY is a rare cause of monogenic diabetes among Brazilian patients.•The molecular analysis of the PDX1 revealed six variants in patients from Brazil.•The rare c.532G > A p.(Glu178Lys) seems to be a cause of PDX1-MODY in the family described here.