Marle N, Martinet D, Aboura A, Joly-Helas G, Andrieux J, Flori E, Puechberty J, Vialard F, Sanlaville D, Fert Ferrer S, Bourrouillou G, Tabet A C, Quilichini B, Simon-Bouy B, Bazin A, Becker M, Stora H, Amblard S, Doco-Fenzy M, Molina Gomes D, Girard-Lemaire F, Cordier M P, Satre V, Schneider A, Lemeur N, Chambon P, Jacquemont S, Fellmann F, Vigouroux-Castera A, Molignier R, Delaye A, Pipiras E, Liquier A, Rousseau T, Mosca A L, Kremer V, Payet M, Rangon C, Mugneret F, Aho S, Faivre L, Callier P
Département de Génétique, Hôpital Le Bocage, Université de Bourgogne, Dijon, France.
Clin Genet. 2014 Mar;85(3):233-44. doi: 10.1111/cge.12138. Epub 2013 Apr 5.
Small supernumerary marker chromosomes (sSMCs) are structurally abnormal chromosomes that cannot be characterized by karyotype. In many prenatal cases of de novo sSMC, the outcome of pregnancy is difficult to predict because the euchromatin content is unclear. This study aimed to determine the presence or absence of euchromatin material of 39 de novo prenatally ascertained sSMC by array-comparative genomic hybridization (array-CGH) or single nucleotide polymorphism (SNP) array. Cases were prospectively ascertained from the study of 65,000 prenatal samples [0.060%; 95% confidence interval (CI), 0.042-0.082]. Array-CGH showed that 22 markers were derived from non-acrocentric markers (56.4%) and 7 from acrocentic markers (18%). The 10 additional cases remained unidentified (25.6%), but 7 of 10 could be further identified using fluorescence in situ hybridization; 69% of de novo sSMC contained euchromatin material, 95.4% of which for non-acrocentric markers. Some sSMC containing euchromatin had a normal phenotype (31% for non-acrocentric and 75% for acrocentric markers). Statistical differences between normal and abnormal phenotypes were shown for the size of the euchromatin material (more or less than 1 Mb, p = 0.0006) and number of genes (more or less than 10, p = 0.0009). This study is the largest to date and shows the utility of array-CGH or SNP array in the detection and characterization of de novo sSMC in a prenatal context.
小额外标记染色体（sSMC）是无法通过核型分析进行特征描述的结构异常染色体。在许多新发sSMC的产前病例中，由于常染色质含量不明，妊娠结局难以预测。本研究旨在通过阵列比较基因组杂交（array-CGH）或单核苷酸多态性（SNP）阵列确定39例产前确诊的新发sSMC中常染色质物质的有无。这些病例是从对65000份产前样本的研究中前瞻性确定的[0.060%；95%置信区间（CI），0.042 - 0.082]。阵列比较基因组杂交显示，22个标记源自非近端着丝粒标记（56.4%），7个源自近端着丝粒标记（18%）。另外10例仍未明确（25.6%），但其中10例中的7例可通过荧光原位杂交进一步鉴定；69%的新发sSMC含有常染色质物质，其中95.4%为非近端着丝粒标记。一些含有常染色质的sSMC具有正常表型（非近端着丝粒标记为31%，近端着丝粒标记为75%）。常染色质物质的大小（大于或小于1 Mb，p = 0.0006）和基因数量（大于或小于10个，p = 0.0009）在正常和异常表型之间显示出统计学差异。本研究是迄今为止规模最大的，显示了阵列比较基因组杂交或SNP阵列在产前背景下检测和鉴定新发sSMC中的作用。
