title: Phenotypic variability in 49 cases of ESCO2 mutations, including novel missense and codon deletion in the acetyltransferase domain, correlates with ESCO2 expression and establishes the clinical criteria for Roberts syndrome.
abstract: 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. Of 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.
  
  
  OBJECTIVE
  To provide unpublished clinical data for 31 patients with proven ESCO2 mutations and combine this series with previously reported clinical and mutation data on 18 cases. Methods Genotype-phenotype correlations and functional effects of two novel ESCO2 mutations were analysed. In situ hybridisation on human embryos at Carnegie stages 14, 17 and 21 was performed to study ESCO2 expression during development.
  
  
  CONCLUSIONS
  Using the cohort of 49 patients, the clinical criteria for RBS were delineated to include: growth retardation; symmetric mesomelic shortening of the limbs in which the upper limbs are more commonly and severely affected than the lower limbs; characteristic facies with microcephaly. The severity of malformations of the facies correlates with the severity of limb reduction. The occurrence of corneal opacities may be associated with specific mutations. Two new mutations, both in the ESCO2 acetyltransferase domain, are described and their acetylation effects in vitro demonstrated. In situ hybridisation on human embryos showed ESCO2 expression in the brain, face, limb, kidney and gonads, which corresponds to the structures affected in RBS.
authors: Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine of City University of New York, New York, NY 10029, USA. hhvegaf@unal.edu.co
authors: H
authors: H
authors: Vega
authors: A H
authors: AH
authors: Trainer
authors: M
authors: M
authors: Gordillo
authors: M
authors: M
authors: Crosier
authors: H
authors: H
authors: Kayserili
authors: F
authors: F
authors: Skovby
authors: M L Giovannucci
authors: ML
authors: Uzielli
authors: R E
authors: RE
authors: Schnur
authors: S
authors: S
authors: Manouvrier
authors: E
authors: E
authors: Blair
authors: J A
authors: JA
authors: Hurst
authors: F
authors: F
authors: Forzano
authors: M
authors: M
authors: Meins
authors: K O J
authors: KO
authors: Simola
authors: A
authors: A
authors: Raas-Rothschild
authors: R C M
authors: RC
authors: Hennekam
authors: E Wang
authors: EW
authors: Jabs
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000123:Acetyltransferases / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D003062:Codon / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D017434:Protein Structure, Tertiary / Q000235:genetics; D017384:Sequence Deletion; D013577:Syndrome
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D003062:Codon; D000123:Acetyltransferases; C500785:ESCO2 protein, human