ClinVar

In a Brazilian male infant (patient 5) with a progressive deforming type of osteogenesis imperfecta (OI20; 618644), Moosa et al. (2019) identified homozygosity for a 5-bp deletion (c.607_611del, NM_015154.1) in exon 3 of the MESD gene, causing a frameshift predicted to result in a premature termination codon (Thr203AlafsTer26), removing a highly conserved ER-retention domain. His unaffected consanguineous parents were heterozygous for the mutation, which was not a common polymorphism in the Exome Variant Server, 1000 Genomes Project, dbSNP, ExAC, or gnomAD databases. The patient died of respiratory failure at age 7 months.

In 3 stillborn sibs with OI20, who were born to nonconsanguineous parents of German origin, Sturznickel et al. (2021) identified compound heterozygous mutations in the MESD gene: the c.607_611del mutation in exon 3, and a 1-bp deletion (c.265delG; 607783.0005) in exon 2, resulting in a frameshift and premature termination (Ala89HisfsTer8). The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. Each parent was heterozygous for one of the mutations. Sequencing of the mRNA from the parents revealed a complete loss of the mRNA harboring the c.265del mutation, while the mRNA with the c.607_611del mutation was readily detected. Sturznickel et al. (2021) suggested that the prenatally lethal phenotype in this family was likely related to complete functional loss of one MESD allele, which could not be compensated by the residual function of the second allele.