A unique case of Bloom syndrome with a combination of genetic hits: A lesson from trio-based exome sequencing: A case report

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Authors

WAYHELOVÁ Markéta VALLOVÁ Vladimíra BROŽ Petr MIKULÁŠOVÁ Aneta MACHÁČKOVÁ Dominika FILKOVÁ Hana Dynková SMETANA Jan TAKÁCSOVÁ Alena GAILLYOVÁ Renata KUGLÍK Petr

Year of publication 2023
Type Article in Periodical
Magazine / Source Molecular Medicine Reports
MU Faculty or unit

Faculty of Science

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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