Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE. Av. Mariscal Sucre y Av. Mariana de Jesús, Sede Occidental, Bloque I, 2 floor, 170129, Quito, Ecuador.
Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-SACYL-CSIC, Salamanca, Spain.
BMC Med Genomics. 2019 Nov 21;12(1):167. doi: 10.1186/s12920-019-0614-4.
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.
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.
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."
自 1969 年以来，已有 49 例环状染色体 4 的病例被报道。所有这些病例都具有遗传物质的缺失特征。位于这些染色体区域的基因与表型有关。
一名 10 岁的厄瓜多尔混血女孩患有环状染色体 4，对其进行了临床、细胞遗传学和分子分析。临床检查显示存在先天性异常，包括小头畸形、鼻梁突出、小下颌、耳朵低位、第五指双侧弯曲、骶尾部小凹、身材矮小和智力迟钝。细胞遗传学研究显示镶嵌核型，mos 46,XX,r(4)(p16.3q35.2)/46,XX，在十年内进行的三项研究中，环状染色体 4 的比例为 75%至 79%。这些结果通过荧光原位杂交（FISH）得到证实。通过高分辨率图谱定位，发现 4p16.3 缺失 1.7Mb 和获得 342kb，4q35.2 缺失 3Mb。
大多数环状染色体 4 的病例都存在末端区域遗传物质的缺失；然而，我们的病例在环状染色体形成中存在 inv dup del 重排。所有回顾病例的异质性临床特征都与丢失或获得的遗传物质数量有关。应用多种技术可以增加我们对环状染色体 4 及其偏离典型“环状综合征”的认识。
