Panasiuk Barbara, Usinskiené Ruta, Kostyk Ewa, Rybałko Alicja, Stasiewicz-Jarocka Beata, Krzykwa Bogustawa, Pieńkowska-Grela Barbara, Kucinskas Vaidutis, Michalova Kyra, Midro Alina T
Department of Clinical Genetics, Medical University of Bialystok, Poland.
Ann Genet. 2004 Jan-Mar;47(1):11-28. doi: 10.1016/j.anngen.2004.01.001.
A central concept in genetic counselling is the estimation of the probability of occurrence of unbalanced progeny at birth and other unfavourable outcomes of pregnancy (miscarriages, stillbirths and early death). The estimation of the occurrence probability for individual carriers of four different X-autosome translocations with breakpoints at Xp, namely t(X;5)(p22.2;q32), t(X;6)(p11.2;q21), t(X;7)(p22.2;p11.1), and t(X;22)(p22.1;p11.1), is presented. The breakpoint positions of chromosomal translocations were interpreted using GTG, RBG and FISH-wcp. Most of these translocations were detected in women with normal phenotype, karyotyped because of repeated miscarriages and/or malformed progeny. A girl with very rare pure trisomy Xp22.1-->pter and a functional Xp disomy was ascertained in one family and her clinical picture has been described in details. It has been suggested that not fully skewed X chromosome inactivation of X-autosome translocation with breakpoint positions at Xp22 (critical segment) could influence the phenotype and risk value. Therefore, the X inactivation status was additionally evaluated by analysis of replication banding patterns using RBG technique after incorporation of BrdU. In two carriers of translocations: t(X;5)(p22.2;q32) and t(X;7)(p22.2;p11.1), late replication state of der(X) was observed in 5/100 and 10/180 analysed cells, respectively. In these both cases the breakpoint positions were clustered at the critical segment Xp22.2. In two other cases, one with the breakpoint position within [t(X;22)(p22.1;p11.1)] and one outside the critical region [t(X;6)(p11.2;q21)], fully skewed inactivation was seen. Therefore, we suggest that neither the distribution of the breakpoint positions nor fully skewed inactivation influenced the phenotype of observed t(X;A) carriers. The occurrence probabilities of the unbalanced progeny were calculated according to Stene and Stengel-Rutkowski along with application of updated available empirical data. In the studied group the values of occurrence probability for unbalanced offspring at birth ranged from 2.1% to 17%. Information on the magnitude of the individual figures may be important for women carrying a reciprocal X;A translocation when deciding upon further family planning.
遗传咨询中的一个核心概念是估计出生时出现染色体不平衡后代的概率以及妊娠的其他不良结局（流产、死产和早夭）。本文给出了4种不同的X - 常染色体易位（断裂点位于Xp，即t(X;5)(p22.2;q32)、t(X;6)(p11.2;q21)、t(X;7)(p22.2;p11.1)和t(X;22)(p22.1;p11.1)）个体携带者出现相关情况的概率估计。使用GTG、RBG和FISH - wcp对染色体易位的断裂点位置进行了解读。这些易位大多在表型正常的女性中被检测到，她们因反复流产和/或子代畸形而进行了核型分析。在一个家庭中确诊了一名患有非常罕见的纯Xp22.1→pter三体和功能性Xp二体的女孩，并详细描述了她的临床症状。有人提出，断裂点位于Xp22（关键区段）的X - 常染色体易位中，X染色体失活不完全偏斜可能会影响表型和风险值。因此，在掺入BrdU后，通过RBG技术分析复制带型模式，对X失活状态进行了额外评估。在两名易位携带者：t(X;5)(p22.2;q32)和t(X;7)(p22.2;p11.1)中，分别在5/100和10/180个分析细胞中观察到der(X)的晚复制状态。在这两种情况下，断裂点位置都聚集在关键区段Xp22.2。在另外两例中，一例断裂点位置在[t(X;22)(p22.1;p11.1)]内，另一例在关键区域外[t(X;6)(p11.2;q21)]，观察到完全偏斜的失活。因此，我们认为断裂点位置的分布和完全偏斜的失活均未影响观察到的t(X;A)携带者的表型。根据Stene和Stengel - Rutkowski的方法，并应用更新后的可用经验数据，计算了染色体不平衡后代的出现概率。在研究组中，出生时染色体不平衡后代的出现概率值在2.1%至17%之间。这些个体数据的大小信息对于携带相互X;A易位的女性在决定进一步的计划生育时可能很重要。
