利用染色体芯片技术诊断伴肾脏钙质沉着的Williams-Beuren综合征一例

Diagnosis of a case with Williams-Beuren syndrome with nephrocalcinosis using chromosome microarray analysis

目的 探讨1例不明原因生长发育迟缓、肾脏钙质沉着伴听力缺损等多器官系统发育异常患儿的临床表型和遗传学病因.方法 分别采用常规G显带和染色体芯片技术,对2015年9月华中科技大学同济医学院附属同济医院儿科收治的1例不明原因生长发育迟缓、肾脏钙质沉着伴听力缺损等多器官系统发育异常的患儿及其父母进行染色体核型分析和全基因组扫描,继而通过检索Decipher和NCBI数据库查询其缺失的基因,并分析其与临床表型之间的关系.结果 患儿男,6月龄,因不明原因生长发育迟缓,喂养困难就诊.检查：生长发育落后,特殊面容,脐疝,先天性心脏病,甲状腺功能减低,右耳感音神经性聋,高钙血症及肾脏钙质沉着.患儿染色体核型为46,XY,16qh＋,其父母未见明显的染色体异常.染色体芯片分析发现患儿在7q11.23（72701098 _74136633）区域存在大小为1 436 kb的杂合性缺失,缺失区域中包含23个编码蛋白质的基因,上述基因被报道与Williams-Beuren综合征及其部分临床表型可能存在对应关系.患儿父母染色体芯片检查未见明显异常.结论 患儿呈典型Williams-Beuren综合征表型,并存在肾脏钙质沉着等少见表现;利用染色体芯片技术确诊其为Williams-Beuren综合征;患儿7号染色体长臂（7q11.23）上编码基因的缺失与Williams-Beuren综合征的特定临床表型可能存在对应关系.

Objective To explore the clinical phenotypes and the genetic cause for a boy with unexplained growth retardation,nephrocalcinosis,auditory anomalies and multi-organ/system developmental disorders.Method Routine G-banding and chromosome microarray analysis were applied to a child with unexplained growth retardation,nephrocalcinosis,auditory anomalies and multi-organ/system developmental disorders treated in the Department of Pediatrics of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in September 2015 and his parents to conduct the chromosomal karyotype analysis and the whole genome scanning.Deleted genes were searched in the Decipher and NCBI databases,and their relationships with the clinical phenotypes were analyzed.Result A six-month-old boy was refered to us because of unexplained growth retardation and feeding intolerance.The affected child presented with abnormal manifestation such as special face,umbilical hernia,growth retardation,hypothyroidism,congenital heart disease,right ear sensorineural deafness,hypercalcemia and nephrocalcinosis.The child＇s karyotype was 46,XY,16qh＋,and his parents＇ karyotypes were normal.Chromosome microarray analysis revealed a 1 436 kb deletion on the 7q1 1.23 （72701098_74136633） region of the child.This region included 23 protein-coding genes,which were reported to be corresponding to Williams-Beuren syndrome and its certain clinical phenotypes.His parents＇ results of chromosome microarray analysis were normal.Conclusion A boy with characteristic manifestation of Williams-Beuren syndrome and rare nephrocalcinosis was diagnosed using chromosome microarray analysis.The deletion on the 7q1 1.23 might be related to the clinical phenotypes of Williams-Beuren syndrome,yet further studies are needed.