Patients with Novo Mutation in ASXL2

Today “The American Journal of Human Genetics” published the discovery of the first patients with De Novo Truncating Variants in ASXL2.  Vandana Shashi, a professor of pediatrics for the Division of Medical Genetics at Duke University School of Medicine, and colleagues present the first patient with De Novo Truncating Variants in ASXL2. Within a few weeks five additional children, all with the same physical features and the ASXL2 gene mutation were found throughout GeneMatcher. However the new disease has no name yet, Shashi said: “We can now definitively say this is a newly identified disease, [… .] With just one case, we could not say the gene mutation was the underlying cause. But with six cases, all with the same ASXL2 mutation, it is definitive.”  ASXL2 belongs to the same gene family as ASXL1 gene and ASXL3 gene. Mutations in ASXL1 and ASXL3 have been respectively implicated in causing Bohring-Opitz Syndrome (BOS) and Bainbridge-Ropers syndrome (BRS) with overlapping symptoms of severe intellectual disability and dysmorphic features but more severe impairments than patients with De Novo Truncating Variant in ASXL2. These six patients have overlapping characteristics with Bohring-Opitz Syndrome, like prominent eyes, arched eyebrows, hypertelorism, a glabellar nevus flammeus, neonatal feeding difficulties and hypotonia. Different from BOS and BRS patients with ASXL2 mutation have features like macrocephaly, absence of growth retardation and more variability in the degree of intellectual disabilities.

» Shashi, VandanaBacino, A. et al.: De Novo Truncating Variants in ASXL2 Are Associated with a Unique and Recognizable Clinical Phenotype. The American Journal of Human Genetics DOI: