Interdepartment of Biomedical Sciences, Faculty of Graduate School, Chulalongkorn University, Bangkok 10330, Thailand.
BMC Med Genet. 2011 Mar 31;12:46. doi: 10.1186/1471-2350-12-46.
The presence of mammary glands distinguishes mammals from other organisms. Despite significant advances in defining the signaling pathways responsible for mammary gland development in mice, our understanding of human mammary gland development remains rudimentary. Here, we identified a woman with bilateral amastia, ectodermal dysplasia and unilateral renal agenesis. She was found to have a chromosomal balanced translocation, 46,XX,t(1;20)(p34.1;q13.13). In addition to characterization of her clinical and cytogenetic features, we successfully identified the interrupted gene and studied its consequences.
Characterization of the breakpoints was performed by molecular cytogenetic techniques. The interrupted gene was further analyzed using quantitative real-time PCR and western blotting. Mutation analysis and high-density SNP array were carried out in order to find a pathogenic mutation. Allele segregations were obtained by haplotype analysis.
We enabled to identify its breakpoint on chromosome 1 interrupting the protein tyrosine receptor type F gene (PTPRF). While the patient's mother and sisters also harbored the translocated chromosome, their non-translocated chromosomes 1 were different from that of the patient. Although a definite pathogenic mutation on the paternal allele could not be identified, PTPRF's RNA and protein of the patient were significantly less than those of her unaffected family members.
Although ptprf has been shown to involve in murine mammary gland development, no evidence has incorporated PTPRF in human organ development. We, for the first time, demonstrated the possible association of PTPRF with syndromic amastia, making it a prime candidate to investigate for its spatial and temporal roles in human breast development.
乳腺的存在将哺乳动物与其他生物区分开来。尽管在确定负责小鼠乳腺发育的信号通路方面取得了重大进展，但我们对人类乳腺发育的理解仍然很初级。在这里，我们鉴定了一位双侧乳房发育不全、外胚层发育不良和单侧肾发育不全的女性。她被发现存在染色体平衡易位，46,XX,t(1;20)(p34.1;q13.13)。除了对其临床和细胞遗传学特征进行表征外，我们还成功鉴定了中断的基因并研究了其后果。
通过分子细胞遗传学技术对断裂点进行了表征。使用定量实时 PCR 和 Western blot 进一步分析中断的基因。为了寻找致病突变，进行了突变分析和高密度 SNP 阵列分析。通过单体型分析获得等位基因分离。
我们能够鉴定出染色体 1 上的断点，该断点中断了蛋白酪氨酸受体 F 基因（PTPRF）。虽然患者的母亲和姐妹也携带易位染色体，但她们的非易位染色体 1 与患者的不同。尽管无法确定父本等位基因上的明确致病突变，但患者的 PTPRF RNA 和蛋白明显少于未受影响的家庭成员。
虽然已经表明 ptprf 参与了小鼠乳腺发育，但没有证据表明 PTPRF 参与了人类器官发育。我们首次证明了 PTPRF 与综合征性乳房发育之间的可能关联，使其成为研究其在人类乳房发育中的时空作用的主要候选基因。
