title: Expanding the mutation and clinical spectrum of Roberts syndrome.
abstract: Roberts syndrome and SC phocomelia syndrome are rare autosomal recessive genetic disorders representing the extremes of the spectrum of severity of the same condition, caused by mutations in ESCO2 gene. We report three new patients with Roberts syndrome from three unrelated consanguineous Egyptian families. All patients presented with growth retardation, mesomelic shortening of the limbs more in the upper than in the lower limbs and microcephaly. Patients were subjected to clinical, cytogenetic and radiologic examinations. Cytogenetic analysis showed the characteristic premature separation of centromeres and puffing of heterochromatic regions. Further, sequencing of the ESCO2 gene identified a novel mutation c.244_245dupCT (p.T83Pfs*20) in one family besides two previously reported mutations c.760_761insA (p.T254Nfs*27) and c.764_765delTT (p.F255Cfs*25). All mutations were in homozygous state, in exon 3. The severity of the mesomelic shortening of the limbs and craniofacial anomalies showed variability among patients. Interestingly, patient 1 had abnormal skin hypopigmentation. Serial fetal ultrasound examinations and measurements of long bones diagnosed two affected fetuses in two of the studied families. A literature review and case comparison was performed. In conclusion, we report a novel ESCO2 mutation and expand the clinical spectrum of Roberts syndrome.
authors.affiliation: Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
authors.forename: Hanan H
authors.initials: HH
authors.lastname: Afifi
authors.affiliation: Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
authors.forename: Ghada M H
authors.initials: GM
authors.lastname: Abdel-Salam
authors.affiliation: Human Cytogenetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
authors.forename: Maha M
authors.initials: MM
authors.lastname: Eid
authors.affiliation: Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Angie M S
authors.initials: AM
authors.lastname: Tosson
authors.affiliation: Chemistry Department, Biochemistry Unit, Faculty of Science, Helwan University, Cairo, Egypt.
authors.forename: Wafaa Gh
authors.initials: WG
authors.lastname: Shousha
authors.affiliation: Ophthalmic Genetics Department, Research Institute of Ophthalmology, Cairo, Egypt.
authors.forename: Amira A
authors.initials: AA
authors.lastname: Abdel Azeem
authors.affiliation: Prenatal Diagnosis and Fetal Medicine Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
authors.forename: Mona K
authors.initials: MK
authors.lastname: Farag
authors.affiliation: Orodental Genetics Department, Oral and Dental Research Division, National Research Centre, Cairo, Egypt.
authors.forename: Mennat I
authors.initials: MI
authors.lastname: Mehrez
authors.affiliation: Prenatal Diagnosis and Fetal Medicine Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
authors.forename: Khaled R
authors.initials: KR
authors.lastname: Gaber
mesh_terms: D000123:Acetyltransferases / Q000235:genetics; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D003241:Consanguinity; D019465:Craniofacial Abnormalities / Q000175:diagnosis* / Q000235:genetics*; D004252:DNA Mutational Analysis; D004480:Ectromelia / Q000175:diagnosis* / Q000235:genetics*; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D006972:Hypertelorism / Q000175:diagnosis* / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D009154:Mutation; D010641:Phenotype; D011859:Radiography
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D000123:Acetyltransferases; C500785:ESCO2 protein, human
keywords: ESCO2 novel mutation; RBS/SC complex; Roberts syndrome; prenatal diagnosis