Hanson et al. (2009) ascertained 10 probands with the 3M syndrome phenotype in whom direct DNA sequencing failed to detect mutations in the CUL7 gene (609577). All patients had short stature, prominent heels, and a distinctive facial appearance ... Hanson et al. (2009) ascertained 10 probands with the 3M syndrome phenotype in whom direct DNA sequencing failed to detect mutations in the CUL7 gene (609577). All patients had short stature, prominent heels, and a distinctive facial appearance with anteverted nares, fleshy tipped nose, frontal bossing, midface hypoplasia, and prominent heels, and were phenotypically indistinguishable from those with 3M syndrome-1.
By genomewide linkage analysis, followed by candidate gene sequencing of 10 unrelated families with 3M syndrome-2, Hanson et al. (2009) identified homozygous or compound heterozygous mutations in the OBSL1 gene (see, e.g., 610991.0001-610991.0005) in affected individuals. All of ... By genomewide linkage analysis, followed by candidate gene sequencing of 10 unrelated families with 3M syndrome-2, Hanson et al. (2009) identified homozygous or compound heterozygous mutations in the OBSL1 gene (see, e.g., 610991.0001-610991.0005) in affected individuals. All of the mutations were truncating mutations within the first 6 exons of the gene and affected all known isoforms, resulting in complete loss of OBSL1. Thus, 3M syndrome-2 represents the null phenotype of human OBSL1. Knockdown of OBSL1 via siRNAs in HEK cells led to a decrease in CUL7 levels, suggesting a role for OBSL1 in the maintenance of normal levels of CUL7. These findings suggested that the 2 proteins work in the same pathway that affects cell proliferation and human growth.