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.

Background: X-linked intellectual disability type Nascimento (XIDTN), caused by mutations in ubiquitin-conjugating enzyme E2A (UBE2A) gene, is characterized by moderate to severe intellectual disability, impaired speech, urogenital anomalies, skin abnormalities, and dysmorphic facial features.

Methods: Whole-exome sequence was carried out in the patients, and the variant of disease-associated gene in the patient and his parents was confirmed by Sanger sequencing. RNA transcript analysis by reverse transcription (RT)-PCR was performed to assess the potential effects of the splice site mutation.

Results: A novel splicing mutation (c.331-2A>G) in UBE2A gene, inherited from his mother, was identified in a Chinese boy with intellectual disability and impaired speech. Furthermore, brain magnetic resonance imaging showed multiple patchy hyperintensity in bilateral centrum ovale. RT-PCR demonstrated that this variant generated a novel transcript with a deletion of 29 nucleotides in exon 6 (r.331_359del), resulting in a frameshift mutation (p.L112SfsX17).

Conclusion: Ultimately, he was diagnosed with XIDTN by genetic analysis. To the best of our knowledge, this is the first case report of this syndrome in China with a confirmed molecular diagnosis. Our case not only expands the mutation spectrum of UBE2A, but also provides additional insights into the genetic and phenotypic heterogeneity of XIDTN as well as phenotype-genotype correlations in this disease.