HAKM Using long read sequencing to phase variant in patients with hyperinsulinism

A single genetic typo can cause Schaaf-Yang syndrome, but only if it sits on the copy of the *MAGEL2* gene inherited from the father—the mother’s copy is naturally switched off. This project will use long-read sequencing to read through both parental copies of the gene in a single stretch, allowing researchers to tell which parent a patient’s variant came from. Currently, around half of Schaaf-Yang cases arise from new mutations, while the other half are inherited. Because a variant on the silenced maternal copy causes no disease, the condition can appear to skip generations, leaving families uncertain about recurrence risks. Standard short-read sequencing often cannot assign a variant to a specific parent, making diagnosis ambiguous. If this approach works, it will turn a diagnostic guessing game into a definitive test. Clinicians could confidently diagnose Schaaf-Yang syndrome, distinguish inherited from *de novo* cases, and give families accurate genetic counselling. The method could also be applied to other imprinting disorders where parent-of-origin determines disease, improving diagnostic yield across a class of conditions that currently frustrate standard sequencing.