目的 探讨Snijders Blok-Campeau综合征(SBCS)患儿的临床表型和基因变异特点。 方法 选取2017年6月于河南省儿童医院被确诊为SBCS的1例患儿为研究对象。收集患儿的临床病例资料，采集患儿及其父母的外周血样提取基因组DNA，进行家系全外显子组测序(trio-WES)及基因组拷贝数变异(CNV)检测，针对可疑致病变异位点，应用Sanger测序进行家系验证。 结果 患儿主要临床表现为语言障碍、智力障碍和运动发育迟缓，伴特殊面容(前额宽、面部呈倒三角状、眉毛稀疏、眼距宽、眼裂小、鼻梁宽、面中部凹陷、上唇薄、尖下颌、耳位低且耳壳后旋)。trio-WES和Sanger测序结果提示患儿存在CHD3基因c.4073-2A>G杂合剪接变异，其父母均为野生型，CNV检测未发现致病性CNV。 结论 该SBCS患儿临床特征为语言和智力障碍、运动发育迟缓，伴特殊面容。CHD3基因剪接变异可能为导致该患儿罹患SBCS的遗传学病因。 Objective To analyze the clinical phenotype and genetic variant of a child with Snijders Blok-Campeau syndrome (SBCS). Methods A child who was diagnosed with SBCS in June 2017 at Henan Children′s Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and the extraction of genomic DNA, which was subjected to trio-whole exome sequencing (trio-WES) and genome copy number variation (CNV) analysis. Candidate variant was verified by Sanger sequencing of his pedigree members. Results The main clinical manifestations of the child have included language delay, intellectual impairment and motor development delay, which were accompanied with facial dysmorphisms (broad forehead, inverted triangular face, sparse eyebrows, widely spaced eyes, narrow palpebral fissures, broad nose bridge, midface hypoplasia, thin upper lip, pointed jaw, low-set ears and posteriorly rotated ears). Trio-WES and Sanger sequencing revealed that the child has harbored a heterozygous splicing variant of the CHD3 gene, namely c. 4073-2A>G, for which both of his parents were of wild-type. No pathogenic variant was identified by CNV testing. Conclusion The c. 4073-2A>G splicing variant of theCHD3 gene probably underlay the SBCS in this patient.
Abstract
Objective To analyze the clinical phenotype and genetic variant of a child with Snijders Blok-Campeau syndrome (SBCS). Methods A child who was diagnosed with SBCS in June 2017 at Henan Children′s Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and the extraction of genomic DNA, which was subjected to trio-whole exome sequencing (trio-WES) and genome copy number variation (CNV) analysis. Candidate variant was verified by Sanger sequencing of his pedigree members. Results The main clinical manifestations of the child have included language delay, intellectual impairment and motor development delay, which were accompanied with facial dysmorphisms (broad forehead, inverted triangular face, sparse eyebrows, widely spaced eyes, narrow palpebral fissures, broad nose bridge, midface hypoplasia, thin upper lip, pointed jaw, low-set ears and posteriorly rotated ears). Trio-WES and Sanger sequencing revealed that the child has harbored a heterozygous splicing variant of the CHD3 gene, namely c. 4073-2A>G, for which both of his parents were of wild-type. No pathogenic variant was identified by CNV testing. Conclusion The c. 4073-2A>G splicing variant of theCHD3 gene probably underlay the SBCS in this patient.
万方数据