Dries David, Baca Katrina, Truss Lisa, Dobin Sheila
The Moran Eye Center, University of Utah, Salt Lake City, UT 84123, USA.
Ophthalmic Genet. 2003 Sep;24(3):175-80. doi: 10.1076/opge.24.3.175.15612.
Abnormalities of chromosome 13 have been associated with bilateral retinoblastoma. Deletion of a retinoblastoma gene is a common primary mechanism. Other abnormalities are more rare. To our knowledge, a balanced translocation of the long arms of the X and 13 chromosomes associated with bilateral retinoblastoma has been reported five times. We report an unbalanced X;13 translocation resulting in partial trisomy 13 and an interstitial deletion of an RB locus.
Case report.
A 19-month-old child presented with seizures to the emergency department. A CT scan revealed bilateral intraocular calcification, and retinoblastoma (RB) was confirmed with an ophthalmic exam. Abnormal facies and developmental delay were noted. A partial trisomy derived from the translocation of X;13 was observed in both bone marrow and peripheral blood cells. Fluorescence in-situ hybridization (FISH) studies confirmed triplication of a region on the q arm of chromosome 13 spanning the RB locus. One of the normal chromosome 13 homologues had an interstitial deletion of the RB locus since no signal was observed for the RB-1 probe despite the visible presence of the 13q14 region. Additional evidence of the interstitial deletion is supported by the typical facial features and developmental delay found. Presumably, the translocated X underwent X inactivation precluding systemic features typically observed in trisomy 13. Parental karyotypes were normal. The chromosomal abnormality was a de-novo constitutional event.
Only two RB loci were present in this patient despite triplication of 13q. The third locus was deleted. We believe that the second locus was not expressed due to X inactivation of the RB gene on the der(X)t(Xq:13q) chromosome. The emergence of bilateral retinoblastoma points towards lack of heterozygosity at the third and last remaining RB loci in tumor cells. To our knowledge, an unbalanced translocation resulting in partial trisomy 13 with retinoblastoma has not been previously reported.
13号染色体异常与双侧视网膜母细胞瘤有关。视网膜母细胞瘤基因缺失是常见的主要机制。其他异常则较为罕见。据我们所知，X和13号染色体长臂的平衡易位与双侧视网膜母细胞瘤相关的情况已报道过5次。我们报告了一例不平衡的X;13易位，导致13号染色体部分三体及RB基因座的中间缺失。
病例报告。
一名19个月大的儿童因癫痫发作被送往急诊科。CT扫描显示双侧眼内钙化，眼科检查确诊为视网膜母细胞瘤（RB）。患儿存在面容异常和发育迟缓。在骨髓和外周血细胞中均观察到源自X;13易位的部分三体。荧光原位杂交（FISH）研究证实13号染色体长臂上跨越RB基因座的区域出现三倍体。正常的13号染色体同源物之一存在RB基因座的中间缺失，因为尽管可见13q14区域，但RB-1探针未观察到信号。所发现的典型面部特征和发育迟缓支持了中间缺失的额外证据。据推测，易位的X染色体发生了X失活，排除了13三体通常观察到的全身特征。父母的核型正常。该染色体异常是一种新发的染色体结构改变。
尽管13q出现三倍体，但该患者仅存在两个RB基因座。第三个基因座缺失。我们认为第二个基因座未表达是由于der(X)t(Xq:13q)染色体上的RB基因发生了X失活。双侧视网膜母细胞瘤的出现表明肿瘤细胞中第三个也是最后剩余的RB基因座缺乏杂合性。据我们所知，此前尚未报道过导致13号染色体部分三体并伴有视网膜母细胞瘤的不平衡易位。
