Background: Roberts syndrome (RBS) and SC phocomelia are caused by mutations in ESCO2, which codes for an acetyltransferase involved in the regulation of sister chromatid cohesion. From 26 mutations described to date only one missense mutation has been reported and all others are predicted to be truncating mutations. Genotype–phenotype analysis has been hampered by limited numbers of patients with clinical information available.
Methods: We provide unpublished clinical data for 31 individuals with proven ESCO2 mutations and combined this series with previously reported clinical and mutation data on 18 cases. We analyzed genotype-phenotype correlations and functional effects of two novel ESCO2 mutations. In situ hybridization on human embryos at Carnegie stages 14, 17, and 21 was performed to study ESCO2 expression during development.
Results and conclusions: Using the cohort of 49 patients, we delineate the clinical criteria for RBS to include: growth retardation, symmetric mesomelic shortening of the limbs in which the upper limbs are more frequently and severely affected than the lower limbs and characteristic facies with microcephaly. The severity of malformations of the facies correlates with the severity of limb reduction. We found that the occurrence of corneal opacities may be associated with specific mutations. We describe two new mutations, both in the ESCO2 acetyltransferase domain and show their acetylation effects in vitro. In situ hybridization on human embryos showed ESCO2 expression in brain, face, limb, kidney and gonads, which corresponds with the structures affected in RBS.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.