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Updated: Jan 1, 2026
A Scalable, Cell-Based Method for the Functional Assessment of Ube3a Variants
Published on: October 10, 2022
Neurodevelopmental profile of siblings with Angelman syndrome due to pathogenic UBE3A variants
A Sadhwani1, J M Willen2,3, H Miller2,4
1Department of Psychiatry, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA.
Background:
Angelman syndrome (AS) is a neurodevelopmental disorder caused by a lack of expression of the maternally inherited UBE3A gene on chromosome 15. Individuals with AS due to a UBE3A mutation are more likely to have siblings who also have AS compared with those with AS due to other cytogenetic/molecular mechanisms, but it is unknown whether the developmental outcome of siblings who have AS is similar.
Methods:
Through an ongoing AS Natural History Study, we identified seven pairs of siblings with AS due to a UBE3A mutation. We compared the neurodevelopment of the first-born and second-born siblings with AS participants who have a UBE3A mutation and have either typically developing siblings or no siblings.
Results:
Second-born AS participants due to a UBE3A mutation were more likely to be diagnosed at an earlier age. With the exception of higher expressive language scores among the second-born participants, no other differences were observed in the developmental and adaptive functioning skills across the different groups.
Conclusions:
The presence of an older sibling with the same neurodevelopmental disorder is associated with an earlier age of diagnosis and may be associated with an improvement in expressive language skills; the developmental outcome of siblings with AS due to a UBE3A mutation is otherwise comparable.
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