A Case of Diabetes Mellitus Type MODY5 as a feature of 17q12 Deletion Syndrome

Maturity onset diabetes of the young (MODY) is characterized by noninsulin-dependent diabetes diagnosed at a young age (<25 years) with an autosomal dominant inheritence. Rare mutations in the hepatocyte nuclear factor-1-beta (HNF1B) gene produce a syndrome that resemble MODY and about half of patients diagnosed with MODY5 (HNF1B mutation) have a a whole gene deletion, called as 17q12 deletion syndrome, is a rare chromosomal anomaly and is typified by deletion of the more than 15 genes including HNF1B resulting in kidney abnormalities and renal cysts and diabetes syndrome and neurodevelepmental or neuropsychiatric disorders. A 12-year-old girl was referred to our clinic, after high blood sugar was detected in the hospital where she suffered with the complaints of poliuria and polydipsia for the last 1 month. Her serum magnessium level was low (1.5 mg/dl) (normal value 1.6–2.6) and HbA1c level was 14% (normal value 3.6–5.8) and c-peptide level was 1.54 ng/ml (normal value 0.8–4). MODY5 was suspected and followed NGS gene panel (ABCC8, BLK, CEL, GCK, HNF1A, HNF1B, HNF4A, INS, KCNJ11, KLF11, NEURODD1, PAX4, PDX1, RFX6, ZFP57, GLIS3, FOXP3, NEUROG3, G6PC2) analysis revealed that there was no any mutation. On follow-up period, her serum magnessium level was low (1.2 mg/dl) and her urinary magnessium excretion was high at 172.5 mg/day. HNF1B gene mutation was considered in the patient with chronic hypomagnesemia with increased basal C peptide level. Abdominal CT and MR imagings revealed that there was a 43 mm diameter cystic lesion in the head of the pancreas, and agenesis of the pancreatic neck, trunk and tail as well. Because of there is no mutation in HBF1B gene in NGS panel, microarray analysis was performed, heterozygous deletion at 17q12 including HNF1B was detected. The HNF1B mutation is difficult to diagnose and has a large phenotypic variation. In case of clinical suspicion,further genetic examination (MLPA, array CGH) may be required since deletions and duplications can not be detected even if mutations in the HNF1B gene are not detected with NGS.