Clinical, cytogenetic, and molecular findings in a patient with ring chromosome 4: case report and literature review

Abstract

Background: Since 1969, 49 cases have been presented on ring chromosome 4. All of these cases have been characterized for the loss of genetic material. The genes located in these chromosomal regions are related to the phenotype. Case presentation: A 10-year-old Ecuadorian Mestizo girl with ring chromosome 4 was clinically, cytogenetically and molecularly analysed. Clinical examination revealed congenital anomalies, including microcephaly, prominent nose, micrognathia, low set ears, bilateral clinodactyly of the fifth finger, small sacrococcygeal dimple, short stature and mental retardation. Cytogenetic studies showed a mosaic karyotype, mos 46,XX,r(4)(p16.3q35.2)/46,XX, with a ring chromosome 4 from 75 to 79% in three studies conducted over ten years. These results were confirmed by fluorescence in situ hybridization (FISH). Loss of 1.7 Mb and gain of 342 kb in 4p16.3 and loss of 3 Mb in 4q35.2 were identified by high-resolution mapping array. Conclusion: Most cases with ring chromosome 4 have deletion of genetic material in terminal regions; however, our case has inv dup del rearrangement in the ring chromosome formation. Heterogeneous clinical features in all cases reviewed are related to the amount of genetic material lost or gained. The application of several techniques can increase our knowledge of ring chromosome 4 and its deviations from typical "ring syndrome."

Rare pathology derived from a ring chromosome 15. Clinical, genomic and protein interactome of genes associated with the phenotype

“…mosómicas (rotura-reunión), y que antiguamente generaron discusiones científicas porque se pensaba que algo tenían que ver con el fenotipo. Este tipo de dinamismo del anillo, se lo puede observar y es gráficamente llamativo, pero no se asocia al fenotipo final 2,6,17 .…”

“…La variabilidad clínica observada en nuestra paciente y en todos los casos informados respondería al tamaño de la pérdida de ADN del cromosoma 15 involucrado en el anillo. Al igual que hemos analizado en otros casos de cromosomas en anillo 2,6,17 , la heterogeneidad clínica y la frecuencia baja de la mayoría de características nos lleva a pensar que es muy difícil describir un fenotipo estándar y conceptualizar un Síndrome del anillo 18 , nos reafirmamos que el fenotipo alterado está definido principalmente por la cantidad de material genético involucrado en la formación del anillo y la pérdida de los genes de la región específica.…”