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2020

ANUÁRIO DO HOSPITAL
DONA ESTEFÂNIA

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A NOVEL MUTATION IN BLM UNDERLYING BLOOM SYNDROME

Leen Moens1, Giorgia Bucciol1, José German Casas Martin1, Ana Isabel Cordeiro2, Conceição Neves2, Catarina Martins3, Isabelle Meyts1, João Farela Neves2,3

1- Primary Immunodeficiencies unit, Leuven University hospital, Belgium
2- Unidade de Imunodeficiências Primárias, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa
3- Center for Chronic Diseases, CEDOC, Nova Medical School, Lisbon

ESID European Society for Immunodeficiencies, apresentação sob forma de poster

Introdução: 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
Métodos: Whole exome sequencing (WES) was performed in a 14-year-old girl with high-pitched voice, long, narrow face, microcephaly, recurrent chest infections, hypogammaglobulinemia, short stature and early-onset type 2 diabetes mellitus. She didn’t have skin manifestations, including the prototypic sun-induced face rash.
Resultados: 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.
Conclusão: We report a novel mutation in BLM in a teenager with some phenotypic manifestations of Bloom syndrome, but lacking the usual skin manifestations.

Palavras Chave: Bloom syndrome, Cancer, DNA repair, Primary Immunodeficiencis