Decoding Variants of Uncertain Significance: Unraveling Rare Genetic Mutations in Neonatal Diabetes
Year: 2025
Type: article
Study design: Case Report
Abstract: Aim and background: Precision medicine plays a critical role in diagnosing neonatal diabetes mellitus.We report the use of molecular genetics to identify a rare variant of uncertain significance (VUS) in the YIPF5 gene.Case description: A 3-month-old male infant presented with diabetic ketoacidosis (DKA) and was diagnosed with new-onset diabetes mellitus.The child was started on intravenous insulin infusion and later transitioned to subcutaneous rapid-acting insulin and long-acting insulin.The management of neonatal diabetes mellitus is challenging, as infants require small, carefully titrated doses based on blood sugar levels and frequency of feeding.Genetic evaluation revealed a novel mutation in the YIPF5 gene in the homozygous state, classified as a VUS.This rare mutation is associated with neonatal diabetes mellitus, epilepsy, developmental delay, and microcephaly.Targeted sequencing of the parents provided additional insights into the VUS classification.Conclusion: A systematic approach to interpreting VUS, incorporating clinical judgment, phenotype analysis, and parental sequencing, is essential. Clinical significance:The effective utilization of precision medicine, supported by clinical acumen, is key to developing long-term management plans for rare conditions.
Authors: Jahnavi Muralikrishnan, Mohana Ganapathy, N Kavitha Bhat
Language: English
Topic: Genomics and Rare Diseases
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4416270332