Mosaic variegated aneuploidy as a novel feature in patients with Mulibrey nanism and TRIM37 variants.

Mulibrey nanism is a rare disorder caused by biallelic tripartite motif containing protein 37 (TRIM37) variants and characterised by prenatal onset growth failure, dysmorphic features, restrictive heart disease and predisposition to tumours. TRIM37 has been linked to regulation of centrosome functions. In chromosomal analysis of two siblings with Mulibrey nanism, we observed mosaic variegated aneuploidies. This prompted us to investigate karyotypes of 10 additional patients with Mulibrey, using fibroblast cultures. In the index patients, the prenatal samples and a postnatal skin biopsy showed a heterogeneous mix of aneuploidies in 7-36% of metaphases. Fibroblast karyotypes of the 10 other patients, who were phenotypically comparable to the index patients, showed clinically relevant, low-level abnormalities in one subject. This is the first report on low-level mosaic aneuploidies in Mulibrey amniocytes and neonatal fibroblasts, detectable by conventional karyotyping. The results are in line with previous observations of segregation errors in human cell lines with TRIM37 defects. Further studies are required to elucidate the prevalence and implications of mosaic aneuploidies in Mulibrey nanism.