Low genetic confirmation rate in South Indian subjects with a clinical diagnosis of maturity-onset diabetes of the young (MODY) who underwent targeted next-generation sequencing for 13 genes.

PURPOSE: To screen for maturity-onset diabetes of the young (MODY) variants in subjects with an early age of onset and positive family history of diabetes mellitus. METHODS: 60 subjects with onset of diabetes between 3 and 30 years of age and parental history (onset < 35 years) of diabetes were recruited after excluding autoimmune, pancreatic and syndromic forms of diabetes. Detailed pedigree chart and clinical data were recorded. MODY genetic testing (MODY 1-13) was performed and variant classification was done adhering to the ACMG guidelines. RESULTS: Baseline characteristics of subjects were as follows: mean age of onset of diabetes 19.9 ± 7 years, mean duration of diabetes 6.3 ± 6.8 years, BMI 23.3 ± 3 kg/m2 and C-peptide 1.56 ± 1.06 nmol/l. Four out of sixty (6.6%) were positive for variants classifiable as pathogenic/likely pathogenic: one patient with HNF4Ac.691C > T, (p.Arg231Trp), two with HNF 1A c.746C > A(p.Ser249Ter) and c.1340C > T(p.Pro447Leu), and one with ABCC8 c.4544C > T (p.Thr1515Met). MODY 1 and MODY 3 variants were documented in the paediatric age group (< 18 years). CONCLUSION: A genetic diagnosis of MODY could be confirmed in only 6.6% (4/60) of patients clinically classifiable as MODY. This is less than that reported in clinically diagnosed MODY subjects of European descent. Newly published population data and more stringent criteria for assessment of pathogenicity and younger age of onset of type 2 diabetes in Indians could have contributed to the lower genetic confirmation rate. Apart from variants in the classical genes (HNF1A, HNF4A), a likely pathogenic variant in a non-classical gene (ABCC8) was noted in this study.

Rupture of bicornuate uterus.

A primigravida aged 20 years was referred to Vydehi Institute of Medical Sciences with diagnosis of 30 weeks of period of gestation with eclampsia and failure to respond to induction with misoprostol and she was on Pritchard regimen for the treatment of eclampsia and there was no response to induction of labour and emergency ultrasound was taken and it showed an extrauterine gestation of 30 weeks gestation with fetal demise and free fluid in peritoneum. A tentative diagnosis of secondary abdominal pregnancy with eclampsia was made and she was taken for emergency laprotomy. Intra operative findings showed haemoperitoneum, fetus with placenta and membranes in the peritoneal cavity, there was bicornuate uterus and right horn was ruptured from the fundus to about 8 cm down in the posterior aspect and ruptured part was sutured in two layers. After securing perfect haemostasis, abdomen was closed. This paper illustrates a case report of uterine anomaly with 30 weeks period of gestation and eclampsia and rupture following induction with prostaglandins.