Expanded phenotypic spectrum in MODY 5 patients with 17q12 deletion syndrome: experience from an Indian tertiary care hospital.

Abstract

To study the clinical and genotypic spectrum of patients with HNF-1ß deletions (MODY 5) at a tertiary care hospital. This study included four patients from the Department of Endocrinology at Sher-i-Kashmir Institute of Medical Sciences Srinagar with a strong clinical suspicion of MODY 5. Genetic analysis, including a monogenic gene panel comprising 78 genes associated with MODY and other similar forms of monogenic diabetes, was done. Dosage analysis of HNF 1B by Multiplex Ligand-dependent Probe Amplification (MLPA) was performed. The mean age of patients was 22.25 years with a male-to-female ratio of 3:1. Associated phenotypic features included neurodevelopmental disorder in all four patients, insulin resistance in two patients (2/4) and alopecia in three patients (3/4). One patient had clinical and biochemical hyperandrogenism. All patients had renal malformations, and one patient had a Mullerian anomaly. Family history was present in 1 patient. All patients had pancreatic abnormalities, the most common type being dorsal agenesis of the pancreas (3/4), followed by annular pancreas (1/4). All patients had a genetic deletion of the gene HNF1B on chromosome 17 with a deletion interval of (?_37686431)_(37745059_?), (?_37687281)-(37744884_?), comprising exons 1 to 9. It is imperative to maintain a high index of suspicion for MODY 5 in patients presenting with renal anomalies and diabetes, even in the absence of a family history. Early identification allows for screening family members and ensures a comprehensive approach to identifying and managing other abnormalities in these patients.