Publication details
A unique case of Bloom syndrome with a combination of genetic hits: A lesson from trio-based exome sequencing: A case report
| Authors | |
|---|---|
| Year of publication | 2023 |
| Type | Article in Periodical |
| Magazine / Source | Molecular Medicine Reports |
| MU Faculty or unit | |
| Citation | |
| Web | https://doi.org/10.3892/mmr.2023.12997 |
| Doi | http://dx.doi.org/10.3892/mmr.2023.12997 |
| Keywords | exome sequencing; BLM gene; Bloom syndrome; cancer-predisposing syndrome; copy-number neutral loss of heterozygosity |
| Description | Pathogenic variants affecting the BLM gene are responsible for the manifestation of extremely rare cancer-predisposing Bloom syndrome. The present study reports on a case of an infant with a congenital hypotrophy, short stature and abnormal facial appearance. Initially she was examined using a routine molecular diagnostic algorithm, including the cytogenetic analysis of her karyotype, microarray analysis and methylation-specific MLPA, however, she remained undiagnosed on a molecular level. Therefore, she and her parents were enrolled in the project of trio-based exome sequencing (ES) using Human Core Exome kit. She was revealed as a carrier of an extremely rare combination of causative sequence variants altering the BLM gene (NM_000057.4), c.1642C>T and c.2207_2212delinsTAGATTC in the compound heterozygosity, resulting in a diagnosis of Bloom syndrome. Simultaneously, a mosaic loss of heterozygosity of chromosome 11p was detected and then confirmed as a borderline imprinting center 1 hypermethylation on chromosome 11p15. The diagnosis of Bloom syndrome and mosaic copy-number neutral loss of heterozygosity of chromosome 11p increases a lifetime risk to develop any types of malignancy. This case demonstrates the trio-based ES as a complex approach for the molecular diagnostics of rare pediatric diseases. |
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