To characterize the clinical and molecular features of a patient with maturity onset diabetes of the young (MODY)5 caused by S148L mutation in hepatocyte nuclear factor 1β (HNF-1β) .

The proband was a 23-year-old male with diabetes onset at ten. At that time, a random blood glucose level of 38 mmol/L and hemoglobin A_1c level of 17.6% were detected. Renal insufficiency and renal dysplasia were present at the same time. There′s no family history of diabetes or renal disease in the pedigree. Although the islet cell antibody was negative, he was diagnosed as type 1 diabetes mellitus (T1DM) on account of low C-peptide level. During the follow up, azoospermia, cysts of seminal vesicle and bilateral acute hydronephrosis occurred. MODY-related genes of the proband and his father as well were sequenced using next-generation sequencing. Literature review was conducted for previously reported cases with the same mutation in HNF-1β.

A mutation in the HNF-1β gene S148L (c.443>T) in exon 2 was identified in the proband, but not in his father. Literature review revealed that there were two mutations S148L and S148W reported in eight cases. Seven of the eight probands had S148L mutation. Renal involvement and early-onset diabetes are typical characteristics of most subjects affected by S148L mutation. Some of them had low birthweight or pancreatic malformation and six cases were the first patients in the family.

Congenital renal abnormality, early-onset of diabetes before age of 25 years and with negative T1DM antibodies probably are important clues for diagnosis of MODY5. Therefore, T1DM antibodies negative juvenile diabetes patients accompanied by abnormalities in kidney, pancreas and genital organs should be suspected for MODY5, even those without family history.

Hepatocyte nuclear factor 1β; Maturity onset diabetes of the young; Missense mutation