RESUMO
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.
Assuntos
Anormalidades Craniofaciais/genética , Ectromelia/genética , Genótipo , Hipertelorismo/genética , Fenótipo , Acetiltransferases/genética , Centrômero/genética , Pré-Escolar , Proteínas Cromossômicas não Histona/genética , Aberrações Cromossômicas , Consanguinidade , Anormalidades Craniofaciais/diagnóstico , Análise Citogenética , Análise Mutacional de DNA , Ectromelia/diagnóstico , Egito , Éxons/genética , Feminino , Genes Recessivos/genética , Humanos , Hipertelorismo/diagnóstico , Hibridização in Situ Fluorescente , Lactente , Deformidades Congênitas dos Membros/genética , Masculino , Reação em Cadeia da Polimerase , Estatística como AssuntoRESUMO
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.
Assuntos
Metaloproteinase 2 da Matriz/genética , Mutação , Osteólise/diagnóstico , Osteólise/genética , Adolescente , Criança , Consanguinidade , Feminino , Humanos , Masculino , Metaloproteinase 2 da Matriz/ultraestrutura , Osteólise/diagnóstico por imagem , Reação em Cadeia da Polimerase , RadiografiaRESUMO
This study presents the prevalence, relative frequency, and analysis of genetic diseases/malformations in 73260 individuals. Cases included were ascertained from: Pediatric outpatient clinics of two governmental hospitals and two primary health care centers (PHCCs) in Giza Governorate; Neonatal intensive care unit (NICU) in the selected hospitals and Outpatients Human Genetics Clinics (NRC). 62819 persons visited the outpatients clinics of selected hospitals and PHCCs in Giza governorate. Out of these persons 731 cases (1.16%) proved to have known genetic disorders or malformations. 7755 neonates were delivered in the selected hospitals. Out of these neonates 666 newborns entered NICU and 3% (20 neonates) of them had genetic or congenital disorders. Also, 2686 patients were ascertained from the Human Genetics Clinics, NRC. The overall parental consanguinity rate among the 3417 diagnosed cases was 55%, ranging from 29.5-75%. The study showed a high prevalence of genetic/malformation disorders among Egyptians, with frequencies comparable to other Arab populations (Tab. 4, Ref. 25). Full Text (Free, PDF) www.bmj.sk.
