Supplementary Material for: Characterization of a de novo Supernumerary Neocentric Ring Chromosome Derived from Chromosome 7

Supernumerary ring chromosomes (SRC) are usually derived from regions adjacent to the centromere. Their identification may be challenging, particularly in case of low mosaicism. Here, we report on a patient who was referred for major in utero growth retardation, severe developmental delay, facial dysmorphism, cleft palate, and hypospadias. The karyotype showed a small SRC in mosaic. The combination of FISH, M-FISH and array-CGH was necessary for a complete characterization of this SRC. M-FISH revealed that the SRC originated from chromosome 7. Array-CGH performed with a 400K oligonucleotide array showed a gain in region 7q22.1q31.1 present in low mosaic. This result was confirmed by FISH using BAC probes specific for chromosome 7. The SRC was a neocentric ring derived from 7q22.1q31.1 and was found in only 8% of the cells. This is the first patient carrying a mosaic neocentric SRC derived from the long arm of chromosome 7. Our study emphasizes the need to combine different techniques and to use adapted bioinformatic tools for low-mosaicism marker identification. It also contributes to the delineation of the partial trisomy 7q phenotype.

超数环染色体（Supernumerary ring chromosomes, SRC）通常起源于着丝粒附近的区域。其鉴定工作往往具有挑战性，尤其是在嵌合比例较低的情况下。本研究报道1例因重度宫内生长迟缓、重度发育迟缓、面部畸形、腭裂及尿道下裂而转诊的患者。核型分析显示该患者存在嵌合型小型超数环染色体。需联合应用荧光原位杂交（Fluorescence in situ hybridization, FISH）、多重荧光原位杂交（Multiplex Fluorescence in situ hybridization, M-FISH）及阵列比较基因组杂交（array-based Comparative Genomic Hybridization, array-CGH），才能对该SRC完成完整的特征鉴定。M-FISH结果显示该SRC起源于7号染色体。采用400K寡核苷酸芯片开展的array-CGH检测显示，患者存在7q22.1-q31.1区域的拷贝数增加，且该异常呈现低嵌合比例。采用针对7号染色体的细菌人工染色体（Bacterial Artificial Chromosome, BAC）探针进行的FISH验证了上述结果。该SRC为起源于7q22.1-q31.1区域的新着丝粒环（neocentric ring），仅在8%的细胞中被检出。本研究报道的病例为全球首例起源于7号染色体长臂的嵌合型新着丝粒环染色体患者。本研究强调，针对低嵌合比例的标记染色体鉴定，需联合应用多种检测技术并适配合适的生物信息学工具。同时，本研究也有助于明确7q部分三体综合征的表型特征。