Identification of a likely pathogenic structural variation in the LAMA1 gene by Bionano optical mapping.
Identification of a likely pathogenic structural variation in the LAMA1 gene by Bionano optical mapping.
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通过 Bionano 光学图谱鉴定 LAMA1 基因中可能的致病性结构变异
DOI：
10.1038/s41525-020-0138-z
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发表时间：
2020
影响因子：
5.3
通讯作者：
Dong M
中科院分区：
文献类型：
--
作者：
Chen M;Zhang M;Qian Y;Yang Y;Sun Y;Liu B;Wang L;Dong M
Bionano光学映射（BOM）的最新进展为确定结构变体（SV）提供了很好的见解，但其在鉴定临床可能致病变体方面的实用性需要进一步证明和证明。在一个连续两次妊娠受脑室扩大影响的家庭中，LAMA 1基因座上的剪接可能致病性变体（NM_005559：c. 4663 + 1 G C），未检测到其他与临床表型相关的致病性变异。通过BOM进行的SV分析揭示了母体样品中LAMA 1基因座处的~48 kb重复。实时定量PCR和桑格测序进一步证实了重复序列为c.859-153_4806 + 910 dup。基于这些变异，我们假设胎儿患有以脑室扩大为表现的Poretti-Boltshauser综合征（PBS）。由于能够确定单核苷酸变异和SV，这里采用的策略可能有助于检测当前常规筛查方法遗漏的病例。此外，我们的研究可能会扩大PBS胎儿的表型谱。
Recent advances in Bionano optical mapping (BOM) provide a great insight into the determination of structural variants (SVs), but its utility in identification of clinical likely pathogenic variants needs to be further demonstrated and proved. In a family with two consecutive pregnancies affected with ventriculomegaly, a splicing likely pathogenic variant at the LAMA1 locus (NM_005559: c. 4663 + 1 G C) inherited from the father was identified in the proband by whole-exome sequencing, and no other pathogenic variant associated with the clinical phenotypes was detected. SV analysis by BOM revealed an ~48 kb duplication at the LAMA1 locus in the maternal sample. Real-time quantitative PCR and Sanger sequencing further confirmed the duplication as c.859-153_4806 + 910dup. Based on these variants, we hypothesize that the fetuses have Poretti-Boltshauser syndrome (PBS) presenting with ventriculomegaly. With the ability to determine single nucleotide variants and SVs, the strategy adopted here might be useful to detect cases missed by current routine screening methods. In addition, our study may broaden the phenotypic spectrum of fetuses with PBS.