Pollin T I, Dobyns W B, Crowe C A, Ledbetter D H, Bailey-Wilson J E, Smith A C
Division of Diabetes, Obesity and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland.
Am J Med Genet. 1999 Aug 6;85(4):369-75.
We studied the pedigrees of 14 families segregating a reciprocal translocation with one breakpoint in chromosome 17p13 and the other in the distal region of another autosome. All 14 were ascertained on the basis of an affected index case: 13 had Miller-Dieker syndrome (MDS) and one had dup(17p). In these 14 families, 38 balanced translocation carriers had 127 pregnancies, corrected for ascertainment bias by the exclusion of all index cases and carriers in the line of descent to the index cases. An abnormal phentotype, unbalanced chromosome constitution, or both, were found in 33 of 127 (26%) pregnancies: 15 of 127 (12%) had MDS and an unbalanced karyotype with del (17p); 9 of 127 (7%) had a less severe phenotype with dup(17p); and 9 were unstudied, although MDS with der(17) was usually suspected based on early death and multiple congenital anomalies. When unexplained pregnancy losses, including miscarriages and stillbirths, were excluded from the total, 33 of 99 (33%) pregnancies were phenotypically or genotypically abnormal. The overall risk of abnormal pregnancy outcome of 26% is in the upper range of the reported risk for unbalanced offspring of carrier parents assessed through liveborn aneuploid offspring [Gardner and Sutherland (1996), Oxford Univ. Press]. The risk increases to 33% when unexplained pregnancy losses are excluded from the total. These results are consistent with Daniel's model of risk based on the size of the unbalanced fragments [Daniel (1985) Clin Genet 28:216-224, Daniel et al. (1989) Am J Med Genet 31:14-53]. Pregnancy losses included 26 miscarriages (20%) and two stillbirths (2%) among the 127 pregnancies, similar to the respective population frequencies of 10-20% and 1%.
我们研究了14个家系，这些家系中存在一种相互易位，其中一个断点在17号染色体短臂1区3带，另一个断点在另一条常染色体的远端区域。所有14个家系均基于一名患病先证者确定：13个家系有米勒 - 迪克尔综合征（MDS），1个家系有17号染色体短臂重复（dup(17p)）。在这14个家系中，38名平衡易位携带者有127次妊娠，通过排除所有先证者及其家系中至先证者的携带者来校正确诊偏倚。在127次妊娠中有33次（26%）出现了异常表型、染色体组成不平衡或两者皆有：127次妊娠中有15次（12%）患有MDS且核型不平衡，伴有17号染色体短臂缺失（del(17p)）；127次妊娠中有9次（7%）表型较轻，伴有17号染色体短臂重复（dup(17p)）；另有9次未进行研究，尽管基于早期死亡和多发先天性畸形通常怀疑患有伴有der(17)的MDS。当将包括流产和死产在内的不明原因妊娠丢失从总数中排除后，99次妊娠中有33次（33%）在表型或基因型上异常。26%的异常妊娠结局总体风险处于通过活产非整倍体后代评估的携带者父母生育不平衡后代的报告风险范围上限[加德纳和萨瑟兰（1996年），牛津大学出版社]。当从总数中排除不明原因妊娠丢失后，风险增至33%。这些结果与丹尼尔基于不平衡片段大小的风险模型一致[丹尼尔（1985年）《临床遗传学》28卷：216 - 224页，丹尼尔等人（1989年）《美国医学遗传学杂志》31卷：14 - 53页]。在127次妊娠中，妊娠丢失包括26次流产（20%）和2次死产（2%），与各自人群中10 - 20%和1%的频率相似。
