Department of Molecular Medicine and Surgery, Karolinska Institutet Stockholm, Karolinska University Hospital, Stockholm, Sweden.
Fertil Steril. 2013 Mar 1;99(3):819-826.e3. doi: 10.1016/j.fertnstert.2012.11.016. Epub 2012 Dec 7.
To investigate a cohort of patients with gonadal disorders of sex development (DSD) for causative CBX2 gene mutations and or gene copy number changes.
Genetic association study.
University laboratory and tertiary university-based referral center.
PATIENT(S): 47 patients with different forms of 46,XY or 46,XX gonadal DSD.
INTERVENTION(S): CBX2 gene sequencing and development of a synthetic probe set for multiplex ligation probe amplification (MLPA) to detect CBX2 copy number changes, and reverse-transcriptase polymerase chain reaction (RT-PCR) to evaluate CBX2 expression in two different cell-line types.
MAIN OUTCOME MEASURE(S): Gene sequence alteration and or partial or complete gene copy number variations, and detection of CBX2 mRNA isoforms.
RESULT(S): We detected 10 sequence alterations, 9 reported single nucleotide polymorphisms (SNPs), and a previously unreported variant. This was a silent c.1356G>A transition that may represent a normal variant. A rare SNP (c.1411C>G, p.471Pro>Ala) was found in heterozygous form in one patient. No deletions or duplications were detected by MLPA. Expression of both CBX2 mRNA isoforms was documented in gonadal fibroblasts and Epstein Barr virus (EBV)-transformed lymphocytes.
CONCLUSION(S): No pathogenic CBX2 mutation was detected. Both CBX2 isoforms are expressed in gonadal fibroblasts and EBV-transformed lymphocytes. This study does not support CBX2 gene disruption as a common cause of gonadal DSD.
研究一组性发育障碍（DSD）患者是否存在 CBX2 基因突变和/或基因拷贝数变化的病因。
遗传关联研究。
大学实验室和三级大学转诊中心。
47 名患有不同形式的 46,XY 或 46,XX 性腺 DSD 的患者。
CBX2 基因测序和用于多重连接探针扩增（MLPA）的合成探针集的开发，以检测 CBX2 拷贝数变化，以及逆转录-聚合酶链反应（RT-PCR）以评估两种不同细胞系类型中的 CBX2 表达。
基因序列改变和/或部分或完全基因拷贝数变异，以及 CBX2 mRNA 异构体的检测。
我们检测到 10 个序列改变，9 个报告的单核苷酸多态性（SNP）和一个以前未报道的变异。这是一个沉默的 c.1356G>A 转换，可能代表一个正常变异。在一名患者中发现了一个罕见的 SNP（c.1411C>G，p.471Pro>Ala），呈杂合形式。MLPA 未检测到缺失或重复。在性腺成纤维细胞和 Epstein Barr 病毒（EBV）转化的淋巴细胞中均记录到两种 CBX2 mRNA 异构体的表达。
未检测到致病性 CBX2 突变。两种 CBX2 异构体均在性腺成纤维细胞和 EBV 转化的淋巴细胞中表达。本研究不支持 CBX2 基因缺失是性腺 DSD 的常见原因。
