Rogac Mihael, Kovanda Anja, Lovrečić Luca, Peterlin Borut
Clinical Institute of Genomic Medicine, University Medical Center Ljubljana, Ljubljana, Slovenia.
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Front Genet. 2023 Jul 25;14:1173426. doi: 10.3389/fgene.2023.1173426. eCollection 2023.
Pathogenic genetic variants represent a challenge in prenatal counseling, especially when clinical presentation in familial carriers is atypical. We describe a prenatal case involving a microarray-detected duplication of which causes X-linked Pelizaeus-Merzbacher disease, a progressive hypomyelinating leukodystrophy. Because of atypical clinical presentation in an older male child, the duplication was examined using a novel technology, optical genome mapping, and was found to be an inverted duplication, which has not been previously described. Simultaneously, segregation analysis identified another healthy adult male carrier of this unique structural rearrangement. The novel structural variant was reclassified, and a healthy boy was delivered. In conclusion, we suggest that examining structural variants with novel methods is warranted especially in cases with atypical clinical presentation and may in these cases lead to improved prenatal and postnatal genetic counseling.
致病性基因变异给产前咨询带来了挑战，尤其是当家族携带者的临床表现不典型时。我们描述了一个产前病例，该病例涉及通过微阵列检测到的一个重复，该重复导致X连锁佩利措伊斯-梅茨巴赫病，这是一种进行性低髓鞘性脑白质营养不良。由于一名大龄男童的临床表现不典型，使用一种新技术——光学基因组图谱对该重复进行了检测，结果发现它是一个倒位重复，此前尚未有过相关描述。同时，分离分析确定了另一名携带这种独特结构重排的健康成年男性携带者。这个新的结构变异被重新分类，随后一名健康男婴顺利出生。总之，我们建议，尤其是对于临床表现不典型的病例，有必要采用新方法检测结构变异，这可能会改善这些病例的产前和产后遗传咨询。
