The Impact of Next Generation Sequencing in Diagnosis and Management of Rare Diseases: Bloom Syndrome

Bloom syndrome is an exceptionally rare autosomal recessive disorder characterized by a considerable genomic instability due to the defective DNA damage repair machine. It is caused by biallelic pathogenic variants in the gene encoding for one of the five human RecQ helicases, RECQL3/BLM. The disorder manifests clinically as growth deficiency, skin anomalies, immunodeficiencies, insulin resistance, and a high predisposition to cancers. Less than 300 patients have been reported so far. In this paper, we report on the first Romanian patient of bi-ethnic origin, molecularly diagnosed with Bloom syndrome. As the most severe complications of the disorder are the malignancies, developing even in childhood, an early diagnosis is essential for further surveillance and therapeutic approach of Bloom patients.

[1]  E. Greene,et al.  Bloom helicase mediates formation of large single–stranded DNA loops during DNA end processing , 2022, Nature Communications.

[2]  M. Budisteanu,et al.  Clinical Aspects of a Rare Disease: Bardet Biedl Syndrome , 2022, Medicina Moderna - Modern Medicine.

[3]  S. Sengupta,et al.  Functions of BLM Helicase in Cells: Is It Acting Like a Double-Edged Sword? , 2021, Frontiers in Genetics.

[4]  M. Ababou,et al.  Bloom syndrome and the underlying causes of genetic instability. , 2021, Molecular genetics and metabolism.

[5]  A. Deans,et al.  A Structural Guide to the Bloom Syndrome Complex. , 2020, Structure.

[6]  Š. Pospíšilová,et al.  Diagnosis of Bloom Syndrome in a Patient with Short Stature, Recurrence of Malignant Lymphoma, and Consanguineous Origin , 2020, Molecular Syndromology.

[7]  A. Zauber,et al.  Health supervision for people with Bloom syndrome , 2018, American journal of medical genetics. Part A.

[8]  Robert W. Taylor,et al.  Mutations in TOP3A Cause a Bloom Syndrome-like Disorder , 2024, American journal of human genetics.

[9]  M. B. Karakullukcu,et al.  Bloom syndrome does not always present with sun-sensitive facial erythema. , 2017, European journal of medical genetics.

[10]  B. Zhang,et al.  A helical bundle in the N-terminal domain of the BLM helicase mediates dimer and potentially hexamer formation* , 2017, The Journal of Biological Chemistry.

[11]  E. Imyanitov,et al.  First Two Cases of Bloom Syndrome in Russia: Lack of Skin Manifestations in a BLM c.1642C>T (p.Q548X) Homozygote as a Likely Cause of Underdiagnosis , 2017, Molecular Syndromology.

[12]  D. Amor,et al.  Loss of RMI2 Increases Genome Instability and Causes a Bloom-Like Syndrome , 2016, PLoS genetics.

[13]  N. Ellis,et al.  Bloom's Syndrome: Clinical Spectrum, Molecular Pathogenesis, and Cancer Predisposition , 2016, Molecular Syndromology.

[14]  A. Wagner,et al.  Bloom syndrome in short children born small for gestational age: a challenging diagnosis. , 2013, The Journal of clinical endocrinology and metabolism.

[15]  T. Dörk,et al.  Nonsense mutation p.Q548X in BLM, the gene mutated in Bloom’s syndrome, is associated with breast cancer in Slavic populations , 2012, Breast Cancer Research and Treatment.

[16]  R. Monnat.  Human RECQ helicases: roles in DNA metabolism, mutagenesis and cancer biology. , 2010, Seminars in cancer biology.

[17]  N. Ellis,et al.  Syndrome‐causing mutations of the BLM gene in persons in the Bloom's Syndrome Registry , 2007, Human mutation.

[18]  A. Tomaszewska,et al.  [Chromosome instability syndromes]. , 2006, Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego.

[19]  P. Rigolet,et al.  Structural and functional characterizations reveal the importance of a zinc binding domain in Bloom's syndrome helicase , 2005, Nucleic acids research.

[20]  M. Leppert,et al.  Bloom syndrome: an analysis of consanguineous families assigns the locus mutated to chromosome band 15q26.1. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[21]  D. Bloom.  Congenital telangiectatic erythema resembling lupus erythematosus in dwarfs; probably a syndrome entity. , 1954, A.M.A. American journal of diseases of children.