Supplementary Material for: Olfactory Receptor-Related Duplicons Mediate a Microdeletion at 11q13.2q13.4 Associated with a Syndromic Phenotype

By array-CGH, we identified a cryptic deletion of about 3.4 Mb involving the chromosomal region 11q13.2q13.4 in a child with speech and developmental delay. Highly homologous segmental duplications related to the well-known olfactory receptor (OR)-containing clusters at 8p and 4p are located at the breakpoints of the imbalance and may be involved in its occurrence. Although these structural features are known to promote recurrent chromosomal rearrangements and previous studies had included the 11q13.2q13.4 deletion region among those considered potentially more unstable, neither deletions nor duplications of this region had been reported until now. Among the deleted genes, <i>SHANK2</i> might play a role in the phenotype of the patient since it encodes a postsynaptic scaffolding protein similar to <i>SHANK3</i>, whose haploinsufficiency is a well-known cause of severe speech delay and autistic-like behavior, and recently deletions and mutations of <i>SHANK2</i> have been described in patients with an autistic spectrum disorder or mental retardation.

本研究通过阵列比较基因组杂交（array-CGH），在1例伴言语与发育迟缓的患儿中，检出1例涉及染色体区域11q13.2至q13.4、大小约3.4 Mb的隐匿性缺失。与8p和4p区域已明确的含嗅觉受体（olfactory receptor, OR）基因簇高度同源的片段重复序列，位于该染色体失衡的断裂位点处，可能参与了此次缺失的发生。尽管已知这类结构特征可促进复发性染色体重排，且既往研究已将11q13.2至q13.4缺失区域纳入潜在高不稳定区域之列，但截至目前，该区域的缺失或重复变异均未见文献报道。在此次缺失的基因中，<i>SHANK2</i>基因可能与患儿的临床表型相关，因其编码一种与<i>SHANK3</i>相似的突触后支架蛋白；而<i>SHANK3</i>的单倍剂量不足是已知的严重言语延迟及类孤独症行为的常见病因，且近期已有研究报道，携带<i>SHANK2</i>缺失或突变的患者可表现为孤独症谱系障碍或智力障碍。