Autosomal recessive mutations in BLM underlie Bloom syndrome, a prototypical chromosomal instability syndrome resulting in growth retardation, cancer and immunodeficiency. Other features include a typical face, various skin lesions, diabetes mellitus, and infertility. To date, more than 60 pathogenic variants in BLM have been identified. Despite the lack of definitive treatment, early diagnosis is crucial for optimal follow-up of patients, especially regarding their increased cancer susceptibility.
Whole exome sequencing (WES) was performed in a 14-year-old girl with high-pitched voice, long and narrow face, microcephaly, recurrent respiratory tract infections, hypogammaglobulinemia, short stature and early-onset type 2 diabetes mellitus. She didn’t have skin manifestations, including the prototypic sun-induced face rash.
WES identified a novel private homozygous variant in BLM (p.L753X), causing a stop gain in the DNA helicase domain and predicted to be pathogenic by in silico prediction methods (CADD score 38, MSC 0.08). Functional validation of the variant is ongoing.
We report a novel mutation in BLM in a teenager with some phenotypic manifestations of Bloom syndrome, but lacking the usual skin manifestations.