Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
BMC Med Genomics. 2014 Apr 22;7:19. doi: 10.1186/1755-8794-7-19.
2q37 deletion syndrome is a rare congenital disorder that is characterized by facial dysmorphism, obesity, vascular and skeletal malformations, and a variable degree of intellectual disability. To date, common but variable phenotypes, such as skeletal or digit malformations and obesity, have been associated with the deleted size or affected genes at chromosome 2q37. However, it remains elusive whether 2q37 deletion per se or other genetic factors, such as copy number variations (CNVs), may confer the risk for the tumorigenic condition.
We report a two-year-old Japanese boy with 2q37 deletion syndrome who exhibited the typical facial appearance, coarctation of the aorta, and a global developmental delay, while lacking the symptoms of brachydactyly and obesity. He developed a sex cord-stromal tumor of the right testis at three months of age. The array comparative genome hybridization analysis identified an 8.2-Mb deletion at 2q37.1 (chr2:234,275,216-242,674,807) and it further revealed two additional CNVs: duplications at 1p36.33-p36.32 (chr1:834,101-2,567,832) and 20p12.3 (chr20:5,425,762-5,593,096). The quantitative PCRs confirmed the heterozygous deletion of HDAC4 at 2q37.3 and duplications of DVL1 at 1q36 and GPCPD1 at 20p12.3.
This study describes the unique phenotypes in a boy with 2q37 deletion and additional CNVs at 1p36.33-p36.32 and 20p12.3. The data provide evidence that the phenotypic variations and unusual complications of 2q37 deletion syndrome are not simply explained by the deleted size or genes located at 2q37, but that external CNVs may account at least in part for their variant phenotypes. Accumulating the CNV data for chromosomal disorders will be beneficial for understanding the genetic effects of concurrent CNVs on the syndromic phenotypes and rare complications.
2q37 缺失综合征是一种罕见的先天性疾病，其特征为面部畸形、肥胖、血管和骨骼畸形以及不同程度的智力障碍。迄今为止，常见但具有变异性的表型，如骨骼或指（趾）畸形和肥胖，与 2q37 缺失的大小或受影响的基因相关。然而，2q37 缺失本身或其他遗传因素（如拷贝数变异）是否会导致肿瘤发生的情况仍不清楚。
我们报告了一例两岁的日本男孩患有 2q37 缺失综合征，他表现出典型的面部特征、主动脉缩窄和全面发育迟缓，而没有短指（趾）和肥胖的症状。他在三个月大时右侧睾丸发生了性索-间质细胞瘤。阵列比较基因组杂交分析确定了 2q37.1 处的 8.2-Mb 缺失（chr2：234,275,216-242,674,807），并进一步发现了两个额外的拷贝数变异：1p36.33-p36.32 处的重复（chr1：834,101-2,567,832）和 20p12.3 处的重复（chr20：5,425,762-5,593,096）。定量 PCR 证实了 2q37.3 处 HDAC4 的杂合性缺失以及 1q36 处 DVL1 和 20p12.3 处 GPCPD1 的重复。
本研究描述了一名患有 2q37 缺失和 1p36.33-p36.32 及 20p12.3 额外拷贝数变异的男孩的独特表型。数据表明，2q37 缺失综合征的表型变异和不寻常并发症不能简单地用缺失大小或位于 2q37 的基因来解释，外部拷贝数变异至少部分解释了它们的变异表型。积累染色体疾病的拷贝数变异数据将有助于理解并发拷贝数变异对综合征表型和罕见并发症的遗传影响。
