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.

Biosciences Institute Newcastle University Newcastle upon Tyne NE2 4HH United Kingdom

Department of Experimental Biology Faculty of Science Masaryk University 61137 Brno Czech Republic

Department of Medical Genetics and Genomics University Hospital Brno 62500 Brno Czech Republic

Laboratory of Cytogenomics Centre of Molecular Biology and Genetics Department of Internal Medicine Hematology and Oncology University Hospital Brno 62500 Brno Czech Republic

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