Clinical and genetic study of a Chinese pedigree of pancreatic duodenal homologous box 1 gene mutation with hyperglycemia in pregnancy

Abstract

Objective To retrospectively study the clinical manifestations and molecular genetics of a pedigree of pancreatic duodenal homeobox 1 (PDX1) gene mutation with hyperglycemia in pregnancy. Methods We reported a family with hyperglycemia discovered during pregnancy. The proband showed hyperglycemia and malnutrition during pregnancy. The next generation sequencing of target genes of monogenic diabetes was performed and then Sanger sequencing to verify the suspected gene. Frequency and species conservation of the mutation site was analyzed. Mutation Taster, Polyphen-2, FATHMM and other software was performed for bioinfor matics analysis. Classification for pathogenicity was determined according to the American Society of Medical Genetics and Genomics. Treatment strategy was adjusted for the proband according to the gene result. We reviewed the literature of PDX1 gene mutation in hyperglycemia during pregnancy. Results A PDX1 gene mutation (p.D64E) was detected in the proband. It is a novel mutation and highly conserved in species. The mutation was co-segregated with the clinical phenotypes of diabetes within the pedigrees. In addition to the defects of β-cell function, the proband also suffered from pancreatic exocrine dysfunction. After insulin and trypsin supplementation, her weight increased and the biochemical indicators returned to normal. It is reported in the literature that PDX1 gene mutations in the Caucasian population can lead to hyperglycemia during pregnancy and poor perinatal outcomes. Conclusion Our study firstly indicated that mutations in the PDX1 gene could result in hyperglycemia during pregnancy in Chinese population, suggesting that pancreatic exocrine function should be evaluated in these patients. Trypsin replacement should be prescribed in time to achieve precision therapy. Meanwhile, this study also suggests the importance of establishing screening methods for monogenetic diabetes in hyperglycemic patients during pregnancy. Key words: Diabetes mellitus, gestational; Pancreatic and duodenal homeobox 1; Maturity-onset diabetes of the young