Bloom syndrome is an autosomal recessive disorder characterized by prenatal and postnatal growth deficiency, photosensitive skin changes, immune deficiency, insulin resistance, and a greatly increased risk of early-onset cancer and development of multiple malignancies. Loss-of-function variants of the BLM gene, which codes for a RecQ helicase, cause Bloom syndrome. We report a consanguineous family, with 2 siblings showing clinical signs of suspected chromosome breakage disorder. One of them developed recurrent malignant lymphoma during lifetime. We performed next-generation sequencing analysis, focusing on cancer predisposition syndromes. We identified a homozygous pathogenic nonsense variant c.1642C>T (p.Gln548*) in the BLM gene in the proband, associated with Bloom syndrome. Sanger sequencing validated the presence of a homozygous pathogenic variant in the proband and also in the brother with short stature. In this article, we will focus on the clinical presentation of the syndrome in this particular family as well as the characteristics of malignancies found in the proband.

Central European Institute of Technology Masaryk University Brno Czech Republic

Department of Internal Medicine Hematology and Oncology University Hospital Brno Brno Czech Republic

Department of Pulmonary Diseases and Tuberculosis University Hospital Brno Czech Republic

Faculty of Medicine Masaryk University Brno Czech Republic

Outpatient Ward for Genetics Hospital Jihlava Jihlava Czech Republic

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Arora H, Chacon AH, Choudhary S, McLeod MP, Meshkov L, et al. Bloom syndrome. Int J Dermatol. (2014);53:798–802. PubMed

Berger C, Frappaz D, Leroux D, Blez F, Vercherat M, et al. Wilms tumor and Bloom syndrome (in French) Arch Pediatr. (1996);3:802–805. PubMed

Cairney AE, Andrews M, Greenberg M, Smith D, Weksberg R. Wilms tumor in three patients with Bloom syndrome. J Pediatr. (1987);111:414–416. PubMed

Cunniff C, Bassetti JA, Ellis NA. Bloom's syndrome: clinical spectrum, molecular pathogenesis, and cancer predisposition. Mol Syndromol. (2017);8:4–23. PubMed PMC

Cunniff C, Djavid AR, Carrubba S, Cohen B, Ellis NA, et al. Health supervision for people with Bloom syndrome. Am J Med Genet A. (2018);176:1872–1881. PubMed

Dembowska-Baginska B, Perek D, Brozyna A, Wakulinska A, Olczak-Kowalczyk D, et al. Non-Hodgkin lymphoma (NHL) in children with Nijmegen Breakage syndrome (NBS) Pediatr Blood Cancer. (2009);52:186–190. PubMed

Diaz A, Vogiatzi MG, Sanz MM, German J. Evaluation of short stature, carbohydrate metabolism and other endocrinopathies in Bloom's syndrome. Horm Res. (2006);66:111–117. PubMed

Ellis NA, Groden J, Ye TZ, Lennon DJ, et al. The Bloom's syndrome gene product is homologous to RecQ helicases. Cell. (1995);83:655–666. PubMed

Fedhila-Ben Ayed F, Douira-Khomsi W, Rhayem S, Jelassi M, Zribi H, et al. Burkitt lymphoma in a child with Bloom syndrome. Arch Pediatr. (2016);23:382–384. PubMed

Flanagan M, Cunniff CM. Bloom syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, et al., editors. GeneReview ® [Internet] (University of Washington, Seattle 1993−2020) Initial posting; 2006. March 22 last update: Feb 14, 2019.

Foretová L, Petráková K. Hereditární nádorová onemocnění V. Klin Onkol. (2019);32((Suppl))

German J. Bloom's syndrome. I. Genetical and clinical observations in the first twenty-seven patients. Am J Hum Genet. (1969);21:196–227. PubMed PMC

German J, Sanz MM, Ciocci S, Ye TZ, Ellis NA. Syndrome-causing mutations of the BLM gene in persons in the Bloom's Syndrome Registry. Hum Mut. (2007);28:743–753. PubMed

Gretzula JC, Hevia O, Weber PJ. Bloom's syndrome. J Am Acad Dermatol. (1987);17:479–488. PubMed

Jastaniah W. Successful treatment of mature B-cell lymphoma with rituximab-based chemotherapy in a patient with Bloom syndrome. Pediatr Blood Cancer. (2017);64 PubMed

Karow JK, Chakraverty RK, Hickson ID. The Bloom's syndrome gene product is a 3′-5′ DNA helicase. J Biol Chem. (1997);272:30611–30614. PubMed

Kaseb H, Hozayen S. Chromosome Instability Syndromes, in StatPearls [Internet] Treasure Island (FL): StatPearls Publishing; (2019). PubMed

Kleinberger J, Maloney KA, Pollin TI, Jeng LJ. An openly available online tool for implementing the ACMG/AMP standards and guidelines for the interpretation of sequence variants. Genet Med. (2016);18:1165. PubMed PMC

Masmoudi A, Marrakchi S, Kamoun H, Chaaben H, Ben Salah G, et al. Clinical and laboratory findings in 8 patients with Bloom's syndrome. J Dermatol Case Rep. (2012);6:29–33. PubMed PMC

McGowan J, Maize J, Cook J. Lupus-like histopathology in Bloom syndrome: reexamining the clinical and histologic implications of photosensitivity. Am J Dermatopathol. (2009);31:786–791. PubMed

Nair G, Lobo I, Jayalaksmi TK, Uppe A, Jindal S, et al. Bloom syndrome with lung involvement. Lung India. (2009);26:92–94. PubMed PMC

Prokofyeva D, Bogdanova N, Dubrowinskaja N, Bermisheva M, Takhirova Z, et al. Nonsense mutation p.Q548X in BLM, the gene mutated in Bloom's syndrome, is associated with breast cancer in Slavic populations. Breast Cancer Res Treat. (2013);137:533–539. PubMed

Relhan V, Sinhan S, Bhatnagar T, Garg VK, Kochhar A. Bloom syndrome with extensive pulmonary involvement in a child. Indian J Dermatol. (2015);60:217. PubMed PMC

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. (2015);17:405–424. PubMed PMC

Seemanová E, Seeman P, Jarolím P. Význam syndromů chromozomální instability. Čas Lék Čes. (2002);141:16–22. PubMed

Shahrabani-Gargir L, Shomrat R, Yaron Y, Orr-Urtreger A, Groden J, Legum C. High frequency of a common Bloom syndrome Ashkenazi mutation among Jews of Polish origin. Genet Test. (1998);2:293–296. PubMed

Sokolenko AP, Iyevleva AG, Preobrazhenskaya EV, Mitiushkina NV, Abysheva SN, et al. High prevalence and breast cancer predisposing role of the BLM c.1642C>T (Q548X) mutation in Russia. Int J Cancer. (2012);130:2867–2873. PubMed

Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. (2016);127:2375–2390. PubMed PMC

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