Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun;11(2):73-82.
doi: 10.1159/000507006. Epub 2020 Mar 21.

Diagnosis of Bloom Syndrome in a Patient with Short Stature, Recurrence of Malignant Lymphoma, and Consanguineous Origin

Jakub Trizuljak  1   2   3 , Terezie Petruchová  1 , Ivona Blaháková  2   3 , Zuzana Vrzalová  2   3 , Věra Hořínová  4 , Martina Doubková  5 , Jozef Michalka  1   2 , Jiří Mayer  1   2   3 , Šárka Pospíšilová  1   2   3 , Michael Doubek  1   2   3
Affiliations

Diagnosis of Bloom Syndrome in a Patient with Short Stature, Recurrence of Malignant Lymphoma, and Consanguineous Origin

Jakub Trizuljak et al. Mol Syndromol. 2020 Jun.

Abstract

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.

Keywords: Autosomal recessive variant; BLM; Bloom syndrome; Consanguinity; Lymphoma.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Picture of the proband with short stature and facial dysmorphism. Note the narrow, prolonged face, protruding nose, and retrognathia.
Fig. 2
Fig. 2
Picture of the sibling with short stature and facial dysmorphism. Note the prolonged face, abnormal chin, and high forehead.
Fig. 3
Fig. 3
Pedigree of the consanguineous family with Bloom syndrome showing the obligate carriers and the potential founding mutation carrier.
Fig. 4
Fig. 4
Analysis of the c.1642C>T pathogenic variant (g.100183535C>T) by Integrative Genomics Viewer (green box). Forward sequencing reads are in blue; reverse sequencing reads are in pink.
Fig. 5
Fig. 5
Sanger sequencing results of homozygous c.1642C>T pathogenic variant compared with wild type.
Fig. 6
Fig. 6
Metaphase nuclei of the proband showing acquired chromosomal aberrations.
Fig. 7
Fig. 7
Metaphase nuclei of the sibling showing acquired chromosomal aberrations. Frequency of breakages is much lower than in the proband.
See this image and copyright information in PMC

References

    1. Arora H, Chacon AH, Choudhary S, McLeod MP, Meshkov L, et al. Bloom syndrome. Int J Dermatol. (2014);53:798–802. - PubMed
    1. 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
    1. 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
    1. Cunniff C, Bassetti JA, Ellis NA. Bloom's syndrome: clinical spectrum, molecular pathogenesis, and cancer predisposition. Mol Syndromol. (2017);8:4–23. - PMC - PubMed
    1. 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