PDF(Pubmed)
Abstract：
BACKGROUND: The 18q- deletion syndrome is a rare congenital chromosomal disorder caused by a partial deletion of the long arm of chromosome 18. The diagnosis of a patient with this syndrome relies on the family medical history, physical examination, developmental assessment, and cytogenetic findings. However, the phenotype of patients with 18q- deletion syndrome can be highly variable, ranging from almost normal to severe malformations and intellectual disability, and normal cytogenetic findings are common, thus complicating the diagnosis. Interestingly, only few characteristic features of typical 18q- deletion syndrome were found in the patient, despite sharing the same critical region. To our knowledge, this is the first report of a Malaysian individual with 18q- terminal microdeletion diagnosed with microarray-based technology.
METHODS: Here we report a 16-year-old Malaysian Chinese boy, a product of a non-consanguineous marriage, who presented with intellectual disability, facial dysmorphism, high arched palate, congenital talipes equinovarus (clubfoot), congenital scoliosis, congenital heart defect, and behavioral problems. A routine chromosome analysis on 20 metaphase cells showed a normal 46, XY G-banded karyotype. Array-based comparative genomic hybridization was performed using a commercially available 244 K 60-mer oligonucleotide microarray slide according to the manufacturer\'s protocol. This platform allows genome-wide survey and molecular profiling of genomic aberrations with an average resolution of about 10 kB. In addition, multiplex ligation-dependent probe amplification analysis was carried out using SALSA MLPA kit P320 Telomere-13 to confirm the array-based comparative genomic hybridization finding. Array-based comparative genomic hybridization analysis revealed a 7.3 MB terminal deletion involving chromosome band 18q22.3-qter. This finding was confirmed by multiplex ligation-dependent probe amplification, where a deletion of ten probes mapping to the 18q22.3-q23 region was detected, and further multiplex ligation-dependent probe amplification analysis on his parents showed the deletion to be de novo.
CONCLUSIONS: The findings from this study expand the phenotypic spectrum of the 18q- deletion syndrome by presenting a variation of typical 18q- deletion syndrome features to the literature. In addition, this case report demonstrated the ability of the molecular karyotyping method, such as array-based comparative genomic hybridization, to assist in the diagnosis of cases with a highly variable phenotype and variable aberrations, such as 18q- deletion syndrome.
METHODS: Here we report a 16-year-old Malaysian Chinese boy, a product of a non-consanguineous marriage, who presented with intellectual disability, facial dysmorphism, high arched palate, congenital talipes equinovarus (clubfoot), congenital scoliosis, congenital heart defect, and behavioral problems. A routine chromosome analysis on 20 metaphase cells showed a normal 46, XY G-banded karyotype. Array-based comparative genomic hybridization was performed using a commercially available 244 K 60-mer oligonucleotide microarray slide according to the manufacturer\'s protocol. This platform allows genome-wide survey and molecular profiling of genomic aberrations with an average resolution of about 10 kB. In addition, multiplex ligation-dependent probe amplification analysis was carried out using SALSA MLPA kit P320 Telomere-13 to confirm the array-based comparative genomic hybridization finding. Array-based comparative genomic hybridization analysis revealed a 7.3 MB terminal deletion involving chromosome band 18q22.3-qter. This finding was confirmed by multiplex ligation-dependent probe amplification, where a deletion of ten probes mapping to the 18q22.3-q23 region was detected, and further multiplex ligation-dependent probe amplification analysis on his parents showed the deletion to be de novo.
CONCLUSIONS: The findings from this study expand the phenotypic spectrum of the 18q- deletion syndrome by presenting a variation of typical 18q- deletion syndrome features to the literature. In addition, this case report demonstrated the ability of the molecular karyotyping method, such as array-based comparative genomic hybridization, to assist in the diagnosis of cases with a highly variable phenotype and variable aberrations, such as 18q- deletion syndrome.
摘要：
背景：18q缺失综合征是一种罕见的先天性染色体疾病，由18号染色体长臂的部分缺失引起。这种综合征患者的诊断依赖于家族病史，体检,发展评估，和细胞遗传学发现。然而,18q缺失综合征患者的表型可以是高度可变的，从几乎正常到严重的畸形和智力残疾，正常的细胞遗传学发现是常见的，从而使诊断复杂化。有趣的是,在患者中发现典型的18q缺失综合征的特征很少，尽管共享相同的关键区域。据我们所知,这是首次报道一名马来西亚患者使用基于微阵列的技术诊断为18q末端微缺失。
方法：这里我们报告一个16岁的马来西亚华裔男孩，非近亲婚姻的产物,提出智力残疾的人，面部畸形,高拱形腭，先天性马蹄内翻足(马蹄内翻足),先天性脊柱侧凸,先天性心脏病,和行为问题。对20个中期细胞的常规染色体分析显示正常的46，XYG条带核型。根据制造商的方案，使用市售的244K60聚体寡核苷酸微阵列载玻片进行基于阵列的比较基因组杂交。该平台允许以大约10kB的平均分辨率对基因组畸变进行全基因组调查和分子谱分析。此外,使用SALSAMLPA试剂盒P320端粒-13进行多重连接依赖性探针扩增分析,以确认基于阵列的比较基因组杂交发现。基于阵列的比较基因组杂交分析显示7.3MB末端缺失，涉及染色体带18q22.3-qter。这一发现通过多重连接依赖性探针扩增得到证实，其中检测到映射到18q22.3-q23区域的十个探针的缺失，对其父母的进一步多重连接依赖性探针扩增分析表明该缺失是从头的。
结论：这项研究的发现通过向文献呈现典型的18q缺失综合征特征的变异，扩展了18q缺失综合征的表型谱。此外,该病例报告证明了分子核型分析方法的能力，例如基于阵列的比较基因组杂交，为了帮助诊断具有高度可变表型和可变畸变的病例，如18q缺失综合征。
方法：这里我们报告一个16岁的马来西亚华裔男孩，非近亲婚姻的产物,提出智力残疾的人，面部畸形,高拱形腭，先天性马蹄内翻足(马蹄内翻足),先天性脊柱侧凸,先天性心脏病,和行为问题。对20个中期细胞的常规染色体分析显示正常的46，XYG条带核型。根据制造商的方案，使用市售的244K60聚体寡核苷酸微阵列载玻片进行基于阵列的比较基因组杂交。该平台允许以大约10kB的平均分辨率对基因组畸变进行全基因组调查和分子谱分析。此外,使用SALSAMLPA试剂盒P320端粒-13进行多重连接依赖性探针扩增分析,以确认基于阵列的比较基因组杂交发现。基于阵列的比较基因组杂交分析显示7.3MB末端缺失，涉及染色体带18q22.3-qter。这一发现通过多重连接依赖性探针扩增得到证实，其中检测到映射到18q22.3-q23区域的十个探针的缺失，对其父母的进一步多重连接依赖性探针扩增分析表明该缺失是从头的。
结论：这项研究的发现通过向文献呈现典型的18q缺失综合征特征的变异，扩展了18q缺失综合征的表型谱。此外,该病例报告证明了分子核型分析方法的能力，例如基于阵列的比较基因组杂交，为了帮助诊断具有高度可变表型和可变畸变的病例，如18q缺失综合征。
