Kirwan et al. (2012) reported a family in which 3 sibs, aged 11 to 14 years, had early-onset aplastic anemia or pancytopenia and their mother had myelodysplasia. All also had congenital nerve deafness. None were treated for the ... Kirwan et al. (2012) reported a family in which 3 sibs, aged 11 to 14 years, had early-onset aplastic anemia or pancytopenia and their mother had myelodysplasia. All also had congenital nerve deafness. None were treated for the hematologic abnormalities. In a second family, both a mother and daughter had adult-onset myelodysplasia. Neither had deafness, but the daughter had possible labyrinthitis. Neither received treatment.
By whole-exome sequencing, Kirwan et al. (2012) identified a truncating mutation in the SRP72 gene (602122.0001) in 4 affected members of a family with autosomal dominant aplastic anemia/myelodysplasia and congenital deafness. Screening of this gene in 96 additional ... By whole-exome sequencing, Kirwan et al. (2012) identified a truncating mutation in the SRP72 gene (602122.0001) in 4 affected members of a family with autosomal dominant aplastic anemia/myelodysplasia and congenital deafness. Screening of this gene in 96 additional individuals with bone marrow failure identified 1 woman with myelodysplasia who had a heterozygous missense mutation (R207H; 602122.0002); her mother with myelodysplasia also carried the mutation. In vitro functional expression studies showed that both mutant proteins had reduced colocalization with ER markers compared to wildtype. The truncating mutation showed a marked reduction in coprecipitation with 7SL RNA (see, e.g., RN7SL1, 612177), whereas the R207H mutant protein had increased interaction with 7SL RNA. These defects were predicted to interfere with normal functioning of the signal recognition particle, with a failure to arrest cytoplasmic translation or properly translocate peptides within the cell. However, it was unclear how a defect in protein translocation would result in the phenotype.