A Novel Mutation of NONO-Associated X-linked Syndromic Intellectual Developmental Disorder-34 in a Fetus

Abstract Background The NONO gene is located on chromosome Xq13.1 and encodes a nuclear protein involved in RNA synthesis, transcriptional regulation, and DNA repair. Hemizygous loss-of-function variants in NONO reportedly cause X-linked syndromic intellectual developmental disorder-34 (MRXS34) in males. At present, there are few clinical reports related to MRXS34, and the mutation spectrum of NONO-related diseases has not been completely determined. Methods We report the case of a fetus with noncompaction cardiomyopathy, a short anteroposterior diameter of the corpus callosum and relative macrocephaly. Genotyping examination, including chromosome microarray analysis (CMA) and trio-medical exon sequencing, was performed. Results Medical exon sequencing revealed a de novo hemizygous nonsense mutation (c.214 C > T, p.Gln72Ter) in exon 4 of the NONO gene. A review of previous literature suggested that noncompaction cardiomyopathy, abnormalities of the corpus callosum, and macrocephaly are consistent phenotypes of MRXS34. Conclusion The mutation (c.214 C > T, p.Gln72Ter) in the NONO gene was present in a fetus with MRXS34. This study expands the mutation spectrum of NONO-related diseases and enlarges noncompaction cardiomyopathy, abnormalities of the corpus callosum and macrocephaly to the phenotype of MRXS34 in fetuses.