Supplementary Material for: Extensive, 3,8 Mb sized deletion of 22q12 in a patient with bilateral schwannoma, intellectual disability, sensorineural hearing loss and epilepsy

Introduction: In contrast with the well-known and described deletion of the 22q11 chromosome region responsible for DiGeorge syndrome, 22q12 deletions are much rarer. Only a few dozen cases have been reported so far. This region contains genes responsible for cell cycle control, chromatin modification, transmembrane signaling, cell adhesion and neural development, as well as several cancer predisposition genes. Case presentation: We present a patient with cleft palate, sensorineural hearing loss, vestibular dysfunction, epilepsy, mild to moderate intellectual disability , divergent strabism, pes equinovarus, platyspondylia, and bilateral Schwannoma. Using Microarray-based Comparative Genomic Hybridization (aCGH), we identified the de novo 3,8 Mb interstitial deletion at 22q12.1→22q12.3. We confirmed deletion of the critical NF2 region by MLPA analysis. Discussion/Conclusion: Large 22q12 deletion in the proband encases the critical NF2 region, responsible for development of bilateral Schwannoma. We compared the phenotype of the patient with previously reported cases. Interestingly, our patient developed cleft palate even without deletion of the MN1 gene, deemed responsible in previous studies. We also strongly suspect the DEPDC5 gene deletion to be responsible for seizures, consistent with previously reported cases.

引言：与已被充分研究和报道的、可导致迪格奥尔格综合征（DiGeorge syndrome）的22q11染色体区域缺失不同，22q12区域缺失的病例极为罕见。截至目前，全球仅报道了数十例此类病例。该区域包含调控细胞周期、染色质修饰、跨膜信号转导、细胞黏附与神经发育的相关基因，以及多个癌症易感基因。
病例报告：本文报告1例存在下述临床表现的患者：腭裂、感音神经性听力损失、前庭功能障碍、癫痫、轻中度智力障碍、外斜视、马蹄内翻足、扁平椎及双侧神经鞘瘤。本研究团队通过基于微阵列的比较基因组杂交（Microarray-based Comparative Genomic Hybridization，aCGH）技术，鉴定出该患者存在新发的3.8 Mb大小的22q12.1→22q12.3区域中间缺失。随后通过多重连接依赖性探针扩增（Multiplex Ligation-dependent Probe Amplification，MLPA）分析，验证了关键NF2区域的缺失。
讨论与结论：先证者的大片段22q12缺失包含了与双侧神经鞘瘤发生密切相关的关键NF2区域。本研究团队将该患者的表型与既往报道的病例进行了对比分析。值得注意的是，尽管未缺失既往研究中认为与腭裂发病相关的MN1基因，本患者仍出现了腭裂表型。此外，本研究团队高度怀疑DEPDC5基因的缺失与癫痫发作相关，这一发现与既往报道的病例结果一致。