Identification of a likely pathogenic structural variation in the LAMA1 gene by Bionano optical mapping

• DOI: 10.1038/s41525-020-0138-z
• Publication Date: 2020-08-12T10:06:55Z
• Authors: Min Chen; Min Zhang; Yeqing Qian; Yanmei Yang; Yixi Sun; Bei Liu; Liya Wang; Minyue Dong
• Keywords: Sanger sequencing; Proband; Ventriculomegaly

Abstract Recent advances in Bionano optical mapping (BOM) provide a great insight into the determination of structural variants (SVs), but its utility identification clinical likely pathogenic needs to be further demonstrated and proved. In family with two consecutive pregnancies affected ventriculomegaly, splicing variant at LAMA1 locus (NM_005559: c. 4663 + 1 G > C) inherited from father was identified proband by whole-exome sequencing, no other associated phenotypes detected. SV analysis BOM revealed an ~48 kb duplication maternal sample. Real-time quantitative PCR Sanger sequencing confirmed as c.859-153_4806 910dup. Based on these variants, we hypothesize that fetuses have Poretti-Boltshauser syndrome (PBS) presenting ventriculomegaly. With ability determine single nucleotide SVs, strategy adopted here might useful detect cases missed current routine screening methods. addition, our study may broaden phenotypic spectrum PBS.