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.