Frühmesser Anne, Erdel Martin, Duba Hans-Christoph, Fauth Christine, Amberger Albert, Utermann Gerd, Zschocke Johannes, Kotzot Dieter
Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schoepfstr. 41, A-6020 Innsbruck, Austria.
Eur J Med Genet. 2013 Jul;56(7):383-8. doi: 10.1016/j.ejmg.2013.04.003. Epub 2013 Apr 19.
De novo combined duplications/inversions are very rare chromosomal rearrangements. For chromosome 7 just some dozen cases of duplications of various parts of the long arm have been published. We report on a 12-year-old boy with muscular hypotonia, global developmental delay, short stature, and various facial dysmorphism including frontal bossing, temporal narrowing, slightly down-slanting palpebral fissures, a broad nasal root, a long philtrum, a thin and tented upper lip, a drooping lower lip, micrognathia, prominent ears, a short neck, and a low posterior hairline. Karyotype analysis and molecular investigations revealed a complex de novo chromosomal rearrangement on 7q. FISH analysis with locus specific YACs and BACs and SNP array with the Illumina(®) HumanOmni1-Quad v1.0 BeadChip disclosed a direct duplication in the long arm of chromosome 7 (q22.1→q32.2) and an inversion located at the breakpoint between the two copies of the duplication (q31.31→q31.33). In addition, breakpoint characterization at the molecular level revealed a 386 bp insertion carrying two Alu elements of chromosome 19p13.2 between the two copies of the duplication. By a comparison of the SNP haplotypes of the derivative chromosome of the patient and both parents a two-step formation during spermatogenesis was suggested as the most likely mechanism of formation.
新发合并重复/倒位是非常罕见的染色体重排。对于7号染色体，仅发表了十几例长臂各部分重复的病例。我们报告了一名12岁男孩，他有肌张力减退、全面发育迟缓、身材矮小以及各种面部畸形，包括额部隆起、颞部变窄、睑裂轻度向下倾斜、鼻根宽阔、人中长、上唇薄且呈帐篷状、下唇下垂、小颌畸形、耳朵突出、颈部短以及后发际线低。核型分析和分子研究显示7号染色体长臂存在复杂的新发染色体重排。使用位点特异性酵母人工染色体（YAC）和细菌人工染色体（BAC）进行荧光原位杂交（FISH）分析以及使用Illumina（®）HumanOmni1-Quad v1.0 BeadChip进行单核苷酸多态性（SNP）阵列分析，揭示了7号染色体长臂（q22.1→q32.2）的直接重复以及位于重复两份拷贝之间断点处的倒位（q31.31→q31.33）。此外，分子水平的断点特征分析显示，在重复的两份拷贝之间有一个386 bp的插入片段，携带19号染色体p13.2区域的两个Alu元件。通过比较患者及其父母衍生染色体的SNP单倍型，提示精子发生过程中的两步形成是最可能的形成机制。
