RESUMO
Type 1 neurofibromatosis (NF1) is an autosomal dominant disorder with an incidence of about 1 in 3500 live births. Symptoms are highly variable from a few cafè-au-lait spots and axillary freckling to plexiform neurofibromas, optic gliomas, pseudarthrosis, and malignancy. Since disease causing mutations are dispersed throughout the gene, prenatal diagnosis is usually performed in familial cases by linkage analysis and rarely by direct characterization of the mutation. We have characterized 48 families and have performed four prenatal diagnoses. In three cases, the linkage analysis was carried out using informative markers. A direct approach using the protein truncation test (PTT) and sequencing was performed in one case in which a R1947X mutation was identified. The extreme variability of the phenotypic expression of the NF1 gene makes reproductive decisions in NF1 families very difficult, as molecular diagnosis cannot predict clinical expression of the disease. The psychological management of the couple is therefore difficult. In two of the three examined families the reproductive choices were not influenced by the specific manifestations of the disease in that family.
Assuntos
Amostra da Vilosidade Coriônica , Doenças Fetais/diagnóstico , Neurofibromatose 1/diagnóstico , Adulto , Criança , Pré-Escolar , Mapeamento Cromossômico , Análise Mutacional de DNA , Feminino , Doenças Fetais/genética , Genes da Neurofibromatose 1/genética , Aconselhamento Genético , Ligação Genética , Humanos , Itália , Masculino , Neurofibromatose 1/genética , Linhagem , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
A girl carrying a de novo balanced 13-14 robertsonian translocation showed a clinical phenotype with severe hypotonia, hyperextensible joints, frontal bossing, asymmetric face, no mental retardation, severe scoliosis and motor delay. In situ hybridization analysis on chromosome spreads revealed the presence of the two centromeres in the rearranged chromosomes. Molecular analysis on genomic DNA showed the presence in the proposita of two chromosomes 14 of maternal origin and no chromosome 14 from the father indicating a maternal monocentric uniparental disomy for chromosome 14 (mUPD14). Our patient shows several similarities with other reported cases of mUPD14, suggesting imprinting of a region(s) of chromosome 14 and defining a possible mUPD14 Syndrome.