Pebrel-Richard Céline, Kemeny Stéphan, Gouas Laetitia, Eymard-Pierre Eléonore, Blanc Nathalie, Francannet Christine, Tchirkov Andreï, Goumy Carole, Vago Philippe
Cytogénétique Médicale, Univ Clermont1, UFR Médecine, CHU Clermont-Ferrand, CHU Estaing, 1 place Lucie Aubrac, 63003 Clermont-Ferrand Cedex1, France.
Eur J Med Genet. 2012 Nov;55(11):650-5. doi: 10.1016/j.ejmg.2012.06.014. Epub 2012 Jul 14.
Microduplications 22q11.2 have been recently characterized as a new genomic duplication syndrome showing an extremely variable phenotype ranging from normal or mild learning disability to multiple congenital defects and sharing some overlapping features with DiGeorge/velocardiofacial syndrome (DGS/VCFS), including heart defects, urogenital abnormalities and velopharyngeal insufficiency. We present an atypical and inherited 0.8-Mb duplication at 22q11.2, in the distal segment of the DGS/VCFS syndrome typically deleted region (TDR), in a 3-year-old boy with motor delay, language disorders and mild facial phenotype. This 22q11.2 microduplication was identified by MLPA, designed to detect recurrent microdeletions and microduplications of chromosomal regions frequently involved in mental retardation syndromes and was further characterized by aCGH. The duplicated region encompasses 14 genes, excluding TBX1 but including CRKL, ZNF74, PIK4CA, SNAP29 and PCQAP known to contribute to several aspects of the DGS/VCFS phenotype. To the best of our knowledge, only one case of an isolated duplication in the distal segment of the TDR between chromosome 22-specific low-copy repeats B (LCR22-B) and D (LCR22-D) has been published, but the present report is the first one with a detailed description of physical and developmental features in a patient carrying this kind of atypical 22q11.2 duplication. This case illustrates the importance of reporting unusual 22q11.2 duplications to further evaluate the incidence of these rearrangements in the general population and to improve genotype-phenotype correlations and genetic counseling.
22q11.2微重复最近被鉴定为一种新的基因组重复综合征，其表型变化极大，从正常或轻度学习障碍到多种先天性缺陷，并且与DiGeorge/腭心面综合征（DGS/VCFS）具有一些重叠特征，包括心脏缺陷、泌尿生殖系统异常和腭咽功能不全。我们报告了一名3岁男孩，其在DGS/VCFS综合征典型缺失区域（TDR）的远端节段存在一个非典型的、遗传性的22q11.2 0.8-Mb重复，该男孩有运动发育迟缓、语言障碍和轻度面部表型。这个22q11.2微重复通过MLPA鉴定，MLPA旨在检测经常与智力发育迟缓综合征相关的染色体区域的重复性微缺失和微重复，并通过aCGH进一步进行特征分析。重复区域包含14个基因，不包括TBX1，但包括已知对DGS/VCFS表型的多个方面有贡献的CRKL、ZNF74、PIK4CA、SNAP29和PCQAP。据我们所知，仅有一例在22号染色体特异性低拷贝重复序列B（LCR22-B）和D（LCR22-D）之间的TDR远端节段发生孤立重复的病例被报道，但本报告是第一例对携带这种非典型22q11.2重复的患者的身体和发育特征进行详细描述的病例。该病例说明了报告不寻常的22q11.2重复对于进一步评估这些重排在普通人群中的发生率以及改善基因型-表型相关性和遗传咨询的重要性。
