MN1 is encoded by only two exons. A recurrent heterozygous variant p.Arg1295* was observed in 8 out of 21 probands with de novo mutations. All other mutations identified fall in the terminal exon or the extreme 3’ region of exon 1 of the MN1 gene and are therefore predicted to result in escape from nonsense-mediated mRNA decay.
As transcripts containing the mutations are also detected in fibroblasts, it is probable that the condition is not due to MN1 haploinsufficiency but rather the result of dominantly acting C-terminally truncated MN1 protein. Further studies will be required to understand the underlying biological mechanisms.