Medical Research Center, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, China.
Department of Neurology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, China.
BMC Med Genomics. 2021 Apr 9;14(1):99. doi: 10.1186/s12920-021-00945-8.
Potocki-Shaffer syndrome (PSS) is a rare contiguous gene deletion syndrome marked by haploinsufficiency of genes in chromosomal region 11p11.2p12. Approximately 50 cases of PSS have been reported; however, a syndrome with a PSS-like clinical phenotype caused by 11p11.12p12 duplication has not yet been reported.
11p11.12p12 duplication syndrome was identified and evaluated using a multidisciplinary protocol. Diagnostic studies included intelligence testing, thorough physical examination, electroencephalography (EEG), magnetic resonance imaging (MRI) of the brain, ultrasonography, biochemical tests and karyotype analysis. Next-generation sequencing analysis clarified the location of the chromosomal variations, which was confirmed by chromosome microarray analysis (CMA). Whole-exome sequencing (WES) was performed to exclude single nucleotide variations (SNVs). A wider literature search was performed to evaluate the correlation between the genes contained in the chromosomal region and clinical phenotypes.
The proband was a 36-year-old mother with intellectual disability (ID) and craniofacial anomalies (CFA). She and her older son, who had a similar clinical phenotype, both carried the same 11p11.12p12 duplication with a copy number increase of approximately 10.5 Mb (chr11:40231033_50762504, GRCh37/hg19) in chromosome bands 11p11.12p12. In addition, she gave birth to a child with a normal phenotype who did not carry the 11p11.12p12 duplication. By literature research and DECIPHER, we identified some shared and some distinct features between this duplication syndrome and PSS. One or more of ALX4, SLC35C1, PHF21A and MAPK8IP1 may be responsible for 11p11.12p12 duplication syndrome.
We present the first report of 11p11.12p12 duplication syndrome. It is an interesting case worth reporting. The identification of clinical phenotypes will facilitate genetic counselling. A molecular cytogenetic approach was helpful in identifying the genetic aetiology of the patients and potential candidate genes with triplosensitive effects involved in 11p11.12p12 duplication.
波托茨基-沙费尔综合征（PSS）是一种罕见的连续基因缺失综合征，其特征是 11p11.2p12 染色体区域基因的单倍体不足。已经报道了大约 50 例 PSS 病例；然而，由于 11p11.12p12 重复导致具有 PSS 样临床表型的综合征尚未报道。
采用多学科方案对 11p11.12p12 重复综合征进行鉴定和评估。诊断研究包括智力测试、全面体检、脑电图（EEG）、脑磁共振成像（MRI）、超声检查、生化检查和核型分析。下一代测序分析阐明了染色体变异的位置，通过染色体微阵列分析（CMA）得到了确认。进行全外显子组测序（WES）以排除单核苷酸变异（SNVs）。进行了更广泛的文献检索，以评估染色体区域包含的基因与临床表型之间的相关性。
先证者是一位 36 岁的母亲，患有智力障碍（ID）和颅面异常（CFA）。她和她年龄较大的儿子具有相似的临床表型，均携带相同的 11p11.12p12 重复，染色体带 11p11.12p12 中的拷贝数增加约 10.5 Mb（chr11:40231033_50762504，GRCh37/hg19）。此外，她生下了一个表型正常的孩子，没有携带 11p11.12p12 重复。通过文献研究和 DECIPHER，我们确定了该重复综合征与 PSS 之间的一些共同特征和一些独特特征。ALX4、SLC35C1、PHF21A 和 MAPK8IP1 中的一个或多个可能负责 11p11.12p12 重复综合征。
我们首次报道了 11p11.12p12 重复综合征。这是一个值得报告的有趣病例。对临床表型的识别将有助于遗传咨询。分子细胞遗传学方法有助于确定患者的遗传病因和涉及 11p11.12p12 重复的三重复敏感效应的潜在候选基因。
