RESUMEN
NF1 microdeletion syndrome is a common dominant genomic disorder responsible for around 5% of type I neurofibromatosis cases. The majority of cases are caused by mutations arising within the NF1 gene. NF1 microdeletion carriers present a more severe phenotype than patients with intragenic mutations, including mental retardation, cardiac anomalies and dysmorphic features. Here, we report on two brothers with mental retardation presenting a microduplication of the NF1 microdeletion syndrome region detected by array-CGH analysis. Main phenotypic features are mental deficiency, early onset of baldness (15 years old), dental enamel hypoplasia and minor facial dysmorphism. The breakpoint regions coincide with the repeats, and the recombination hot spots shown to mediate NF1 microdeletion through NAHR. A screening of the patients' familial relatives showed that this microduplication segregates in the family for at least two generations. This result demonstrates that both deletion and duplication of the NF1 region, at cytogenetic band 17q11.2, give rise to viable gametes, even if only NF1 microdeletions have been reported until now. Our study reports seven cases of NF1 microduplication within one family. Similar phenotypic abnormalities were present in most of the individuals, however, two displayed a normal phenotype, suggesting a potential incomplete penetrance of the phenotype associated with NF1 microduplication.
Asunto(s)
Alopecia/genética , Hipoplasia del Esmalte Dental/genética , Duplicación de Gen , Genes de Neurofibromatosis 1 , Discapacidad Intelectual/genética , Adulto , Cromosomas Humanos Par 17 , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Linaje , FenotipoAsunto(s)
Médula Ósea/patología , Enfermedades Mielodisplásicas-Mieloproliferativas/diagnóstico , Bazo/patología , Translocación Genética , Autoantígenos/genética , Proteínas de Ciclo Celular/genética , Cromosomas Humanos Par 8 , Cromosomas Humanos Par 9 , Humanos , Janus Quinasa 2/genética , Masculino , Persona de Mediana Edad , Enfermedades Mielodisplásicas-Mieloproliferativas/genéticaRESUMEN
BACKGROUND: Chromosome abnormalities are important prognostic factors in myeloma allowing risk stratification of patients. Different techniques are available for their detection including cytogenetics, Fluorescent In Situ Hybridisation (FISH) and array Competitive Genomic Hybridisation (CGH). This study aimed to assess the validity and usefulness of each technique in a diagnostic setting. METHODS: 112 myeloma cases were analysed by whole bone marrow cytogenetics and by FISH and array CGH performed on purified plasma cell populations. RESULTS: Clonal abnormalities were identified in 30% of cases by cytogenetics and 97% by FISH and array CGH. By combining array and FISH results abnormalities were detected in 99% of cases and, if cytogenetic analysis was also considered, abnormalities were detected in 100% of cases. CONCLUSIONS: Cytogenetic analysis is of limited value in myeloma. Array CGH and FISH are highly specific tests allowing the identification of aberrations in virtually all cases. The two techniques are complementary and need to be combined in order to provide a comprehensive analysis of all clinically relevant aberrations in myeloma.