Variants in the Imprinted IGF2 Gene: A Review and Phasing of De Novo Variants Using Long-Read Sequencing.
Trine Maxel Juul, Susanne Eriksen Boonen, Katja Venborg Pedersen et al.
✦ AI-curated · Sources linked
Case in brief
Two unrelated individuals, a 5-year-old girl and an adult woman, were diagnosed with Silver-Russell syndrome (SRS) and found to have de novo missense variants in IGF2. Their developmental outcomes differed: one had normal development, while the other had intellectual disability. Long-read sequencing, using differentially methylated regions, established the allelic origin of the variants without parental samples. The report also reviewed 20 individuals with IGF2 variants, in whom SRS features were common and other reported traits included developmental delays, under-masculinized male genitalia, limb anomalies, congenital heart defects, variable growth faltering, and intellectual disability.
What made this case unusual
Long-read sequencing determined the parental allelic origin of de novo variants in an imprinted gene without requiring parental samples.
Diagnostic / clinical pearl
In suspected IGF2-related SRS, long-read sequencing with differentially methylated regions can establish the allelic origin of a de novo variant when parental samples are unavailable.
Why it matters
The two individuals’ differing developmental outcomes illustrate that intellectual disability may occur alongside the SRS diagnosis associated with IGF2 variants.