Fernández Raquel M, Sánchez Javier, García-Díaz Lutgardo, Peláez-Nora Yolanda, González-Meneses Antonio, Antiñolo Guillermo, Borrego Salud
Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain.
Am J Med Genet A. 2016 May;170A(5):1268-73. doi: 10.1002/ajmg.a.37559. Epub 2016 Jan 14.
Monosomy 10p is a rare chromosomal disorder with a prevalence <1/1,000,000, in which a terminal or interstitial distal region of chromosome 10 is deleted resulting in a variable phenotype depending on the size of the deletion. Two main phenotypes have been defined depending on the location of the deletion: HDR syndrome (Hypoparathyroidism, sensorineural Deafness, and Renal disease), and DGS2 (DiGeorge syndrome type 2). The vast majority of cases reported so far have resulted from de novo events. Here, we present the first familial presentation of this contiguous gene deletion syndrome, affecting two family members in different generations: a child and his maternal uncle. In both cases, the deletion was due to a malsegregation of a maternal balanced rearrangement, ins(16;10)(q22;p13p15.2). The identification and characterization of this rearrangement was possible using a combination of different genetic analyses such as karyotype, MLPA, FISH, and array CGH. We underline the importance of the present results in terms of genetic and reproductive counseling for the carriers of the balanced rearrangement within the family, and demonstrate again the utility of expanding the genetic studies to the relatives of the affected patients.
10号染色体短臂单体是一种罕见的染色体疾病,患病率小于1/1,000,000,其中10号染色体的末端或中间远端区域缺失,导致取决于缺失大小的可变表型。根据缺失的位置定义了两种主要表型:HDR综合征(甲状旁腺功能减退、感音神经性耳聋和肾脏疾病)和DGS2(2型迪乔治综合征)。迄今为止报道的绝大多数病例是由新发事件引起的。在此,我们展示了这种连续性基因缺失综合征的首例家族性病例,影响了不同代的两名家庭成员:一名儿童及其舅舅。在这两个病例中,缺失是由于母亲的平衡重排ins(16;10)(q22;p13p15.2)的错误分离所致。使用不同的遗传分析方法(如核型分析、MLPA、FISH和阵列比较基因组杂交)相结合,有可能识别和表征这种重排。我们强调了本研究结果对于该家族中平衡重排携带者的遗传和生殖咨询的重要性,并再次证明了将遗传研究扩展到受影响患者亲属的实用性。