Bestetti Ilaria, Sironi Alessandra, Catusi Ilaria, Mariani Milena, Giardino Daniela, Manoukian Siranoush, Milani Donatella, Larizza Lidia, Castronovo Chiara, Finelli Palma
1Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto Auxologico Italiano, via Ariosto 13, 20145 Milan, Italy.
2Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Mol Cytogenet. 2018 Sep 19;11:53. doi: 10.1186/s13039-018-0401-5. eCollection 2018.
The 13q deletion syndrome is a rare chromosome disorder associated with wide phenotypic spectrum, which is related to size and location of the deleted region and includes intellectual disability, growth retardation, craniofacial dysmorphisms, congenital malformations, and increased risk of retinoblastoma.
Here, we report on a teenage boy with a mild phenotype characterized by obesity, hyperactivity, dysphagia, dysgraphia, sleep disturbance, and minor dysmorphic features (round face, bushy eyebrows, and stubby hands). Array Comparative Genomic Hybridization on blood identified a mosaic 13q14.13-13q31.1 deletion, with a mosaicism rate around 40%, which was confirmed by quantitative PCR and interphase Fluorescent In Situ Hybridization (iFISH) on both blood genomic DNA and cultured/uncultured blood lymphocytes, respectively. Conversely, karyotype analysis on blood estimated a mosaicism rate of 24% and iFISH on buccal smears revealed a borderline value of 0.4%, suggesting the absence of 13q deletion in this cell line.
The comparison with previous patients carrying similar deletions informed that the proband clinical presentation is the mildest reported to date, thus supporting the burden of mosaicism in modulating the phenotype also in case of large chromosomal rearrangements. Characterization of further cases by in-depth mosaicism rate in tissues with different embryonic origins might contribute in the future to a better definition of genotype-phenotype correlation, including tumor risk.
13q缺失综合征是一种罕见的染色体疾病，其表型谱广泛，与缺失区域的大小和位置有关，包括智力残疾、生长发育迟缓、颅面畸形、先天性畸形以及视网膜母细胞瘤风险增加。
在此，我们报告一名青少年男性，其具有以肥胖、多动、吞咽困难、书写障碍、睡眠障碍以及轻微畸形特征（圆脸、浓眉和短手）为特征的轻度表型。对血液进行的阵列比较基因组杂交鉴定出一种嵌合型13q14.13 - 13q31.1缺失，嵌合率约为40%，分别通过对血液基因组DNA以及培养/未培养的血液淋巴细胞进行定量PCR和间期荧光原位杂交（iFISH）得以证实。相反，对血液进行的核型分析估计嵌合率为24%，对颊黏膜涂片进行的iFISH显示临界值为0.4%，表明该细胞系中不存在13q缺失。
与先前携带类似缺失的患者进行比较可知，该先证者的临床表现是迄今为止报道的最轻微的，从而支持了在大型染色体重排情况下嵌合现象在调节表型方面的作用。通过对具有不同胚胎起源的组织进行深入嵌合率分析来进一步表征病例，未来可能有助于更好地定义基因型 - 表型相关性，包括肿瘤风险。
