A family with hyperinsulinemia caused by a novel mutation of SLC16A1 gene / 中华内分泌代谢杂志

ABSTRACT

Objective:Congenital hyperinsulinemia is a heterogeneous disorder characterized by severe hypoglycemia due to dysregulated insulin secretion. Sixteen genes have been reported to be associated with congenital hyperinsulinemia. In this study, whole exome sequencing was performed on a patient with obesity, hyperinsulinemia, and postprandial hypoglycemia to further explore its genetic etiology.Methods:The clinical data and peripheral blood of a patient with hyperinsulinemia and his family members were collected. Genomic DNA was extracted from the peripheral blood. Sanger sequencing and pedigree verification were performed on the pathogenic variants filtered by whole-exome sequencing. The function of the mutation sites was analyzed by bioinformatics software.Results:The proband presented with obesity, hyperinsulinemia, and postprandial hypoglycemia, but without exercise-induced hypoglycemia. A heterozygous SCL16A1 gene c. 1259A>G(p.K420R) mutation was identified in the proband. Co-segregated analysis showed that the c. 1259A>G mutation was also found in his father and brother, who had obesity and hyperinsulinemia, which was consistent with autosomal dominant inheritance. The mutation c. 1259A>G was predicted to be pathogenic by the MutationTaster, FATHMM-MKL, PolyPhen2, and CADD programs, and has not been reported in HGDM database yet, which was considered to be a novel mutation.Conclusion:This study reported a patient with hyperinsulinemia caused by a new mutation of SCL16A1 gene, which expanded our understanding of the pathogenic mutation spectrum of hyperinsulinemia.