A novel splice site mutation in the UBE2A gene leads to aberrant mRNA splicing in a Chinese patient with X-linked intellectual disability type Nascimento.
Here, we describe two siblings with X-linked ID and typical clinical features of UBE2A deficiency caused by a novel hemizygous variant, identified by massively parallel sequencing of X-exome.
We propose that RAD6-KCMF1-UBR4 represents a unique new E2-E3 complex that targets unknown N-end rule substrates for lysosome-mediated degradation, and that disruption of this complex via RAD6A mutations could negatively affect neuronal function in XLID patients.
Intragenic mutations of the UBE2A gene, as well as larger deletions of Xq24 encompassing UBE2A have in recent years been associated with a syndromic form of X-linked intellectual disability called UBE2A deficiency syndrome or X-linked intellectual disability type Nascimento (OMIM#300860).
Here, we report on overlapping microdeletions at Xq24 that do not include UBE2A or affect its expression, in patients with non-syndromic ID plus some additional features from three unrelated families.
We identified a series of patients with X-linked intellectual disability presenting mutations in the Rad6a (Ube2a) gene, which encodes for an E2 ubiquitin-conjugating enzyme.
By using an in-house bacterial artificial chromosome-based X-tilling array, we detected a 0.4 Mb novel deletion at Xq24 that included UBE2A in a 4-year-old and 10-month-old boy with mental retardation and various other characteristics inherited from his mother; for example, marked developmental delay, synophrys, ocular hypertelorism, esotropia, low nasal bridge, marked generalized hirsutism and seizure.