Abstract：
Partial deletions at chromosome 7q11.23 are causative for the autosomal-dominant Williams-Beuren syndrome (WBS), whereas the partial duplication of this region leads to the 7q11.23 duplication syndrome. Both syndromes are highly penetrant and occur with a frequency of 1:7500-10,000 (WBS) and 1:13,000-20,000 (7q11.23 duplication syndrome). They are associated with multiple organ defects, intellectual disability, and typical facial dysmorphisms showing broad phenotypic variability. The 7q11.23 region is susceptible to chromosomal rearrangements due to flanking segmental duplications and regions of long repetitive DNA segments. Here, we report on a family with two children affected by WBS and clinically unaffected parents. Interestingly, metaphase fluorescence in situ hybridization (FISH) revealed a deletion on 7q11.23 in the father. Intensive genetic testing, using interphase FISH, whole genome sequencing and optical genome mapping led to the confirmation of a 1.5 Mb deletion at one 7q11.23 allele and the identification of a reciprocal 1.8 Mb duplication at the other allele. This finding is highly important regarding genetic counseling in this family. The father is a silent carrier for two syndromic disorders, thus his risk to transmit a disease-causing allele is 100%. To the best of our knowledge we, here, report on the first case in which the phenotype of a microdeletion/microduplication syndrome was compensated by its reciprocal counterpart.
摘要：
染色体7q11.23的部分缺失是常染色体显性遗传的Williams-Beuren综合征（WBS）的病因，而该区域的部分重复导致7q11.23重复综合征。两种综合征都是高度渗透的，发生频率为1：7500-10,000（WBS）和1：13,000-20,000（7q11.23重复综合征）。它们与多器官缺陷有关，智力残疾,和典型的面部畸形表现出广泛的表型变异性。由于侧翼片段重复和长重复DNA片段的区域，7q11.23区域易受染色体重排的影响。这里,我们报道了一个家庭,该家庭有两个孩子受到WBS的影响,父母在临床上没有受到影响.有趣的是,中期荧光原位杂交（FISH）显示父亲7q11.23缺失。密集的基因检测,使用相间FISH，全基因组测序和光学基因组作图证实了一个7q11.23等位基因的1.5Mb缺失,并鉴定了另一个等位基因的1.8Mb重复.这一发现对于这个家庭的遗传咨询非常重要。父亲是两种综合症的沉默携带者，因此，他传播致病等位基因的风险是100%。据我们所知，在这里，报道了第一例微缺失/微重复综合征的表型通过其相互对应物得到补偿。
