背景:Xq22.1-q22.3缺失是一种罕见的染色体畸变。本研究的目的是确定染色体Xq22.1-q22.3缺失的表型和基因型之间的相关性。
方法:通过拷贝数变异测序(CNV-seq)技术和核型分析鉴定染色体畸变。此外,我们回顾了Xq22.1-q22.3缺失或部分与该区域重叠的缺失的患者,以突出该罕见疾病并分析基因型-表型相关性.
结果:我们描述了一个雌性胎儿,该胎儿是中国家系的“先证者”,并且在染色体Xq22.1-q22.3中带有一个杂合的5.29Mb缺失(GRCh37:chrX:100,460,000-105,740,000),可能会影响从DRP2到NAP1L4P2的98个基因。这种缺失包括7种已知的病态基因:TIMM8A,BTK,GLA,HNRNPH2、GPRASP2、PLP1和SERPINA7。此外,父母的表型正常,智力正常。父系基因型正常。母亲在X染色体中携带相同的缺失。这些结果表明胎儿从母亲那里继承了这种CNV。此外,根据下一代测序(NGS)结果,通过家系分析,发现另外两名健康女性家庭成员携带相同的CNV缺失.据我们所知,该家族是第一个据报道Xq22.1-q22.3缺失最大的谱系,但具有智力正常的正常表型。
结论:我们的发现进一步改善了对染色体Xq22.1-q22.3缺失的基因型-表型相关性的理解。该报告可能为携带相似染色体异常的患者的产前诊断和遗传咨询提供新信息。
Xq22.1-q22.3 deletion is a rare chromosome aberration. The purpose of this study was to identify the correlation between the phenotype and genotype of chromosome Xq22.1-q22.3 deletions.
Chromosome aberrations were identified by copy number variation sequencing (CNV-seq) technology and karyotype analysis. Furthermore, we reviewed patients with Xq22.1-q22.3 deletions or a deletion partially overlapping this region to highlight the rare condition and analyse the genotype-phenotype correlations.
We described a female foetus who is the \"proband\" of a Chinese pedigree and carries a heterozygous 5.29 Mb deletion (GRCh37: chrX: 100,460,000-105,740,000) in chromosome Xq22.1-q22.3, which may affect 98 genes from DRP2 to NAP1L4P2. This deletion encompasses 7 known morbid genes: TIMM8A, BTK, GLA, HNRNPH2, GPRASP2, PLP1, and SERPINA7. In addition, the parents have a normal phenotype and are of normal intelligence. The paternal genotype is normal. The mother carries the same deletion in the X chromosome. These results indicate that the foetus inherited this CNV from her mother. Moreover, two more healthy female family members were identified to carry the same CNV deletion through pedigree analysis according to the next-generation sequencing (NGS) results. To our knowledge, this family is the first pedigree to have the largest reported deletion of Xq22.1-q22.3 but to have a normal phenotype with normal intelligence.
Our findings further improve the understanding of the genotype-phenotype correlations of chromosome Xq22.1-q22.3 deletions.This report may provide novel information for prenatal diagnosis and genetic counselling for patients who carry similar chromosome abnormalities.