A rare combination of MODY5 and duodenal atresia in a patient: a case report

Abstract

Background: Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous group of hereditary diabetes, generally caused by one abnormal gene. MODY5 is caused by mutations of the hepatocyte nuclear factor 1 homeobox β gene (HNF1β), always as a part of Chr17q12 deletion, whereas heterozygous mutation in B lymphocyte kinase (BLK) gene is responsible for MODY11. Case presentation: We report a patient who developed diabetes with a 1.58-Mb Chr17q12 microdeletion and BLK gene c.211G > A mutation using the cytoscan high-density array and whole-exome sequencing analysis. The patient received the surgery at five days after birth for the duodenal atresia and had normal growth postoperatively. Mild elevated liver enzymes were found along with the normal renal function. Quantitative analysis of β-cell function markers, including fasting insulin (< 0.2 mIU/L), fasting C-peptide (0.02 μg/L), postprandial-2 h insulin (< 0.2 mIU/L), and postprandial-2 h C-peptide (0.03 μg/L) suggested a severe loss of insulin secreting capacity. Meanwhile, islet autoantibodies (GADA, IA-2, ICA, and IAA) in the patient's blood appeared negative. Neither dysplasia in other tissues nor abnormality in development and behavior was found. Conclusion: To date, gastrointestinal malformations were extremely rarely reported in patients with MODY. Our clinical report further expands the clinical presentation and variability of MODY5.

Molecular mechanisms of β-cell dysfunction and death in monogenic forms of diabetes

“…The affected individual had insulinopenic diabetes and bilateral renal cists without additional severe phenotypes. The contribution of the BLK mutation to diabetes development in this individual could not be assessed (Du et al, 2020). Altogether, this data indicates that the contribution of BKL variants to the development of MODY still requires validation.…”

“…Moreover, the genome databases also show that the frequency of BLK p.Ala71Thr (c.211G > A) mutation is very low suggesting that this BLK variant may act as benign or a pathological factor depending on if it is combined with other diabetic risk factors (Du et al, 2020).…”

Pregnancy outcome with maternal HNF1B gene mutations and 17q12 deletions

“…Seven infants were born prior to 37 weeks' gestation, there were six term deliveries and there was one neonatal death (Table 3). 4,16,[24][25][26][27] In 26 pregnancies where the infant was affected by 17q12 deletion where the mutation was de novo or where inheritance was uncertain, there were 14 live births, 10 pregnancies were terminated, and outcome was not stated in two pregnancies. 4,16,24,26,28,29 Delivery occurred prior to 37 weeks in three of the eight pregnancies where the gestation of delivery was provided.…”

“…Seven infants were born prior to 37 weeks' gestation, there were six term deliveries and there was one neonatal death (Table 3). 4,16,24–27…”