ABSTRACT
The Roberts syndrome (RBS) is a rare autosomal recessive disorder caused by mutation in ESCO2 gene. Among over 150 reported international cases, 16 cases are Egyptian including the presently reported patients. The current study reports 8 new Egyptian patients from 7 unrelated consanguineous families investigating clinical phenotype as well as cytogenetic changes in all cases and mutational spectrum in 4 cases. Clinical, orodental, cytogenetic and molecular studies were done to investigate genotype/phenotype correlation. Evaluation of the studied 8 patients showed that they all exhibited the main limb and craniofacial features of Roberts syndrome. Cytogenetic studies including centromeric separation and puffing by Giemsa and DAPI stains and for the first time in Egypt analysis for premature centromeric division by FISH showed consistent centromeric separation in all studied cases. Molecular studies of 4 available patients showed that they all have ESCO2 gene mutation. We conclude that RBS has a well-defined clinical spectrum. The cytogenetic changes are due to sister chromatid cohesion defects which lead to mitotic dysfunction. We confirmed previous results of lack of genotype/phenotype correlation. We also confirmed that the severity of limb malformation correlates with craniofacial manifestations. We recommend detailed evaluation of orodental changes for further definition of the phenotype and for proper patient management. We emphasize the need for further studies for the frequency of premature centromeric separation by FISH as a possible indicator of phenotypic severity.
Subject(s)
Craniofacial Abnormalities/genetics , Ectromelia/genetics , Genotype , Hypertelorism/genetics , Phenotype , Acetyltransferases/genetics , Centromere/genetics , Child, Preschool , Chromosomal Proteins, Non-Histone/genetics , Chromosome Aberrations , Consanguinity , Craniofacial Abnormalities/diagnosis , Cytogenetic Analysis , DNA Mutational Analysis , Ectromelia/diagnosis , Egypt , Exons/genetics , Female , Genes, Recessive/genetics , Humans , Hypertelorism/diagnosis , In Situ Hybridization, Fluorescence , Infant , Limb Deformities, Congenital/genetics , Male , Polymerase Chain Reaction , Statistics as TopicABSTRACT
Osteolysis syndromes are rare hereditary disorders characterized by destruction and resorption of affected bones. The current study adds three new patients from two unrelated consanguineous families with a severe form of inherited osteolysis. Clinical examination, radiological, biochemical, ultrastructural and molecular studies were conducted. Clinical and radiological studies suggested the diagnosis of Torg-Winchester syndrome. The three affected patients were homozygous for novel MMP2 gene mutations which confirmed the diagnosis. Our patients are the first to be reported from Egypt thus, supporting the pan ethnic nature of the disease.
