Palumbo Orazio, Palumbo Pietro, Delvecchio Maurizio, Palladino Teresa, Stallone Raffaella, Crisetti Matteo, Zelante Leopoldo, Carella Massimo
Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.
Am J Med Genet A. 2015 Feb;167A(2):438-44. doi: 10.1002/ajmg.a.36872. Epub 2014 Nov 26.
We provide a detailed clinical and molecular characterization of an 11-year-old female patient presenting with neurodevelopmental delay (NDD), intellectual disability (ID), seizures, stereotypies and dysmorphic features. Chromosomal microarrays analysis (CMA) detected a small, rare de novo deletion on chromosome 12q24.31 encompassing 31 protein-coding RefSeq genes and a microRNA. Phenotypic comparison with molecularly well-defined cases previously reported in the literature harboring an overlapping 12q24.31 microdeletion indicate that these patients shared common clinical features including neurodevelopmental delay, intellectual disability and behavioral problems. Also, seizures and dysmorphic features are frequent and a consistent pattern was recognized. Since there are remarkable resemblance between the patient described here and at least another one previously reported, our report is provides supportive evidence for the existence of an emerging syndrome caused by a microdeletion in 12q24.31. We propose a minimal region shared among patients contributing to the etiology of the common clinical features observed suggesting as candidate, for the first time, the gene SETD1B which is a component of a histone methyltransferase complex. In addition, we speculate on the possible contributive role of the MIR4304 to some clinical features observed in our patient. Evaluation of more patients with well-characterized deletions within 12q24.31, as well as careful clinical assessment of them, is needed to corroborate our hypothesis, to perform a more detailed genotype-phenotype correlation and, finally, to fully delineate this emerging microdeletion syndrome.
我们对一名11岁女性患者进行了详细的临床和分子特征分析,该患者表现为神经发育迟缓(NDD)、智力残疾(ID)、癫痫、刻板行为和畸形特征。染色体微阵列分析(CMA)检测到12q24.31染色体上一个小的、罕见的新生缺失,该缺失包含31个蛋白质编码RefSeq基因和一个 microRNA。与文献中先前报道的分子特征明确且存在重叠12q24.31微缺失的病例进行表型比较,结果表明这些患者具有共同的临床特征,包括神经发育迟缓、智力残疾和行为问题。此外,癫痫和畸形特征很常见,且呈现出一种一致的模式。由于此处描述的患者与至少另一例先前报道的患者之间存在显著相似性,我们的报告为12q24.31微缺失导致一种新出现的综合征的存在提供了支持性证据。我们提出了患者之间共有的一个最小区域,该区域导致了所观察到的共同临床特征的病因,首次提出基因SETD1B作为候选基因,它是组蛋白甲基转移酶复合物的一个组成部分。此外,我们推测MIR4304对我们患者中观察到的一些临床特征可能具有的促成作用。需要评估更多12q24.31内具有明确特征缺失的患者,并对他们进行仔细的临床评估,以证实我们的假设,进行更详细的基因型 - 表型相关性分析,并最终全面描述这种新出现的微缺失综合征。