RESUMO
Ellis-van Creveld syndrome is an autosomal recessive disorder mainly characterized by a disproportionate limb dwarfism, chondroectodermal dysplasia, congenital heart disease, postaxial polydactyly, and dysplastic fingernails and teeth. Only 300 cases have been published worldwide. We report a 21-week fetus with rhizomelia and polydactyly detected. Gross photographs, radiologic studies and pathological study were performed leading to the clinico-pathological suspicion of EvC. DNA from fresh fetal tissue was extracted for sequencing the EVC and EVC2 genes. p.W215X and p.R677X mutations were identified in the EVC2 gene in the fetal sample. Parental sample analysis showed the p.W215X mutation to be inherited from the mother and the p.R677X mutation from the father. The clinical information is essential not only to arrive at a correct diagnosis in fetuses with pathologic ultrasound findings, but also to offer a proper genetic counseling to the parents and their relatives.
Assuntos
Doenças do Desenvolvimento Ósseo/diagnóstico , Doenças do Desenvolvimento Ósseo/patologia , Síndrome de Ellis-Van Creveld/diagnóstico , Síndrome de Ellis-Van Creveld/patologia , Polidactilia/diagnóstico , Polidactilia/patologia , Adulto , Autopsia , Doenças do Desenvolvimento Ósseo/complicações , Doenças do Desenvolvimento Ósseo/genética , Síndrome de Ellis-Van Creveld/complicações , Síndrome de Ellis-Van Creveld/genética , Feminino , Fêmur/anormalidades , Fêmur/patologia , Doenças Fetais/diagnóstico , Doenças Fetais/genética , Doenças Fetais/patologia , Testes Genéticos , Idade Gestacional , Humanos , Úmero/anormalidades , Úmero/patologia , Polidactilia/complicações , Polidactilia/genética , Gravidez , Diagnóstico Pré-Natal/métodosAssuntos
Análise Citogenética/métodos , Repetições de Microssatélites/genética , Monossomia/diagnóstico , Aborto Espontâneo/genética , Adulto , Alelos , Aberrações Cromossômicas , Cromossomos Humanos Par 21/genética , Hibridização Genômica Comparativa/métodos , Feminino , Humanos , Cariotipagem/métodos , Masculino , Monossomia/genética , GravidezRESUMO
BACKGROUND: Although single trisomy is the most common chromosomal abnormality observed within first trimester spontaneous abortions (SA) (>50%), double trisomy (DT) ranges from 0.21 to 2.8% in the literature. Since little is known about mechanisms underlying DT, we report the results of our experience with 517 SA, establishing parental origin and cell stage of non-disjunction when possible in DT cases, and making a revision of those previously reported. METHODS: Cytogenetic analysis was performed in all aborted specimens. Quantitative fluorescent PCR (QF-PCR) and multiplex ligation-dependent probe amplification (MLPA) were performed in DT cases in order to assess parental origin and stage of error of aneuploidy in addition to its reliability in detecting aneuploidies. RESULTS: Karyotyping was successful in 321 miscarriages; the rate of DT was 2.18%. Among the seven DT cases reported, three new combinations were found. Maternal origin was established for all DT SA analysed. Meiotic stage of error was presumed meiosis I (MI) for 48,XX+15+22 and 48,XX+8+21, meiosis II (MII) for 48,XXX+18, and MII and MI respectively for 48,XY+18+22. Molecular results agreed with cytogenetic results. CONCLUSIONS: Similar maternal age-related mechanisms could be implicated in both single and double trisomy. Molecular techniques could be useful in diagnosing not only single but multiple aneuploidy and determining its origin. This will improve our knowledge about mechanisms underlying human aneuploidy, and enable appropriate genetic counselling.
Assuntos
Aborto Espontâneo/genética , Trissomia , Adulto , Fatores Etários , Feminino , Humanos , Cariotipagem , Idade Materna , Meiose/fisiologia , Não Disjunção Genética , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: Aneuploidies involve approximately 80% of chromosomal anomalies found in spontaneous miscarriages. Since cytogenetic studies show high rates of failure, we have incorporated the quantitative fluorescent polymerase chain reaction (QF-PCR) technique to the study of numerical chromosome anomalies in miscarriages. METHODS: Multiplex and simple QF-PCR assays have been performed on 160 miscarriage and 34 parental DNA samples analysing specific short tandem repeat (STR) markers for chromosomes 2, 7, 13, 15, 16, 18, 21, 22 and X. Cases successfully karyotyped were used as controls in our study. RESULTS: While maternal contamination could be detected in such cases, a molecular result was obtained for 94% of miscarriages without a cytogenetic one. Thirty-six per cent of them were diagnosed with numerical chromosome anomalies. Parental origin of the extra chromosome and the error stage of meiosis could be also determined. CONCLUSIONS: QF-PCR represents a useful and reliable tool to diagnose aneuploidies in spontaneous miscarriages. It provides information about parental and meiotic origin of anomaly, allowing an appropriate genetic counselling.
