A case of a novel mutation in HNF1β-related maturity-onset diabetes of the young type 5 with diabetic kidney disease complication in a Chinese family.

AIMS: Precise diagnosis of maturity-onset diabetes of the young (MODY) has proven valuable for understanding mechanism of diabetes and selecting optimal therapy. A proband and her mother with diabetic kidney disease (DKD) were studied to investigate potential genes responsible for diabetes and different severity of DKD between the parent and offspring.

METHODS: The family with suspected MODY underwent mutational analyses by the whole exome sequencing (WES). Candidate pathogenic variants were validated by Sanger sequencing and tested for co-segregation. The clinical parameters of subjects were collected from medical records.

RESULTS: A novel missense heterozygous mutation in exon 4 of the hepatocyte nuclear factor 1β (HNF1β), c.1007A > G (p.H336R), was identified in both the proband and her mother. Moreover, comparing the family's WES results, we found that the proband had acquired a KCNQ1 gene mutation from her father and acquired ACE and SORBS1 gene mutations from her mother. These three genes are known susceptibility genes of DKD and may impose additional effects contributing to DKD severity.

CONCLUSIONS: A novel mutation in HNF1β-MODY was identified in a Chinese family complicated with DKD, and the additional effect of pathogenic variants in susceptibility genes was speculated to contribute to DKD severity.