PDF(Pubmed)
Abstract：
BACKGROUND: Antenatal Bartter syndrome is a life-threatening disease caused by a mutation in the MAGED2 gene located on chromosome Xp11. It is characterized by severe polyhydramnios and extreme prematurity. While most reported mutations are located in the exon region, variations in the intron region are rarely reported.
METHODS: In our study, we employed whole exome sequencing and Sanger sequencing to genotype members of this family. Additionally, a minigene assay was conducted to evaluate the impact of genetic variants on splicing.
RESULTS: Our findings reveal a novel intronic variant (NM_177433.3:c.1271 + 4_1271 + 7delAGTA) in intron 10 of the MAGED2 gene. Further analysis using the minigene assay demonstrated that this variant activated an intronic cryptic splice site, resulting in a 96 bp insertion in mature mRNA.
CONCLUSIONS: Our results indicate that the novel intronic variant (c.1271 + 4_1271 + 7delAGTA) in intron 10 of the MAGED2 gene is pathogenic. This expands the mutation spectrum of MAGED2 and highlights the significance of intronic sequence analysis.
METHODS: In our study, we employed whole exome sequencing and Sanger sequencing to genotype members of this family. Additionally, a minigene assay was conducted to evaluate the impact of genetic variants on splicing.
RESULTS: Our findings reveal a novel intronic variant (NM_177433.3:c.1271 + 4_1271 + 7delAGTA) in intron 10 of the MAGED2 gene. Further analysis using the minigene assay demonstrated that this variant activated an intronic cryptic splice site, resulting in a 96 bp insertion in mature mRNA.
CONCLUSIONS: Our results indicate that the novel intronic variant (c.1271 + 4_1271 + 7delAGTA) in intron 10 of the MAGED2 gene is pathogenic. This expands the mutation spectrum of MAGED2 and highlights the significance of intronic sequence analysis.
摘要：
背景：产前Bartter综合征是一种由位于染色体Xp11上的MAGED2基因突变引起的危及生命的疾病。它的特点是严重的羊水过多和极度早产。虽然大多数报道的突变位于外显子区域，内含子区域的变异很少报道。
方法：在我们的研究中，我们采用全外显子组测序和Sanger测序对该家族成员进行基因型分析.此外,我们进行了一个小基因试验来评估遗传变异对剪接的影响.
结果：我们的发现揭示了MAGED2基因内含子10中的一个新的内含子变体（NM_177433.3：c.1271+4_1271+7delAGTA）。使用minigene分析的进一步分析表明，该变体激活了内含子隐蔽剪接位点，导致96bp的成熟mRNA插入。
结论：我们的结果表明，MAGED2基因内含子10中的新型内含子变体（c.12714_12717delAGTA）具有致病性。这扩展了MAGED2的突变谱，突出了内含子序列分析的意义。
方法：在我们的研究中，我们采用全外显子组测序和Sanger测序对该家族成员进行基因型分析.此外,我们进行了一个小基因试验来评估遗传变异对剪接的影响.
结果：我们的发现揭示了MAGED2基因内含子10中的一个新的内含子变体（NM_177433.3：c.1271+4_1271+7delAGTA）。使用minigene分析的进一步分析表明，该变体激活了内含子隐蔽剪接位点，导致96bp的成熟mRNA插入。
结论：我们的结果表明，MAGED2基因内含子10中的新型内含子变体（c.12714_12717delAGTA）具有致病性。这扩展了MAGED2的突变谱，突出了内含子序列分析的意义。
