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

J 2023

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

WAYHELOVÁ, Markéta, Vladimíra VALLOVÁ, Petr BROŽ, Aneta MIKULÁŠOVÁ, Dominika MACHÁČKOVÁ et. al.

Basic information

Original name

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

Authors

WAYHELOVÁ, Markéta (203 Czech Republic, guarantor, belonging to the institution), Vladimíra VALLOVÁ (703 Slovakia, belonging to the institution), Petr BROŽ (203 Czech Republic, belonging to the institution), Aneta MIKULÁŠOVÁ, Dominika MACHÁČKOVÁ (203 Czech Republic, belonging to the institution), Hana Dynková FILKOVÁ, Jan SMETANA (203 Czech Republic, belonging to the institution), Alena TAKÁCSOVÁ, Renata GAILLYOVÁ and Petr KUGLÍK (203 Czech Republic, belonging to the institution)

Edition

Molecular Medicine Reports, Spandidos Publications, 2023, 1791-2997

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10603 Genetics and heredity

Country of publisher

Greece

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.400 in 2022

RIV identification code

RIV/00216224:14310/23:00134634

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.3892/mmr.2023.12997

UT WoS

000973984800001

Keywords in English

exome sequencing; BLM gene; Bloom syndrome; cancer-predisposing syndrome; copy-number neutral loss of heterozygosity

Abstract

V originále

Pathogenic variants affecting the BLM gene are responsible for the manifestation of extremely rare cancer‑predisposing Bloom syndrome. The present study reports on a case of an infant with a congenital hypotrophy, short stature and abnormal facial appearance. Initially she was examined using a routine molecular diagnostic algorithm, including the cytogenetic analysis of her karyotype, microarray analysis and methylation‑specific MLPA, however, she remained undiagnosed on a molecular level. Therefore, she and her parents were enrolled in the project of trio‑based exome sequencing (ES) using Human Core Exome kit. She was revealed as a carrier of an extremely rare combination of causative sequence variants altering the BLM gene (NM_000057.4), c.1642C>T and c.2207_2212delinsTAGATTC in the compound heterozygosity, resulting in a diagnosis of Bloom syndrome. Simultaneously, a mosaic loss of heterozygosity of chromosome 11p was detected and then confirmed as a borderline imprinting center 1 hypermethylation on chromosome 11p15. The diagnosis of Bloom syndrome and mosaic copy‑number neutral loss of heterozygosity of chromosome 11p increases a lifetime risk to develop any types of malignancy. This case demonstrates the trio‑based ES as a complex approach for the molecular diagnostics of rare pediatric diseases.

Links

NU20-07-00145, research and development project

Name: Úloha patogenních genetických variant detekovaných pomocí exomového sekvenování v etiologii dětských neurovývojových onemocnění

Investor: Ministry of Health of the CR, Subprogram 1 - standard

Citovat

WAYHELOVÁ, Markéta, Vladimíra VALLOVÁ, Petr BROŽ, Aneta MIKULÁŠOVÁ, Dominika MACHÁČKOVÁ, Hana Dynková FILKOVÁ, Jan SMETANA, Alena TAKÁCSOVÁ, Renata GAILLYOVÁ and Petr KUGLÍK. A unique case of Bloom syndrome with a combination of genetic hits: A lesson from trio-based exome sequencing: A case report. Molecular Medicine Reports. Spandidos Publications, 2023, vol. 27, No 5, p. 1-9. ISSN 1791-2997. Available from: https://dx.doi.org/10.3892/mmr.2023.12997.

@article{2285057,
   author = {Wayhelová, Markéta and Vallová, Vladimíra and Brož, Petr and Mikulášová, Aneta and Macháčková, Dominika and Filková, Hana Dynková and Smetana, Jan and Takácsová, Alena and Gaillyová, Renata and Kuglík, Petr},
   article_number = {5},
   doi = {http://dx.doi.org/10.3892/mmr.2023.12997},
   keywords = {exome sequencing; BLM gene; Bloom syndrome; cancer-predisposing syndrome; copy-number neutral loss of heterozygosity},
   language = {eng},
   issn = {1791-2997},
   journal = {Molecular Medicine Reports},
   title = {A unique case of Bloom syndrome with a combination of genetic hits: A lesson from trio-based exome sequencing: A case report},
   url = {https://doi.org/10.3892/mmr.2023.12997},
   volume = {27},
   year = {2023}
}

TY  - JOUR
ID  - 2285057
AU  - Wayhelová, Markéta - Vallová, Vladimíra - Brož, Petr - Mikulášová, Aneta - Macháčková, Dominika - Filková, Hana Dynková - Smetana, Jan - Takácsová, Alena - Gaillyová, Renata - Kuglík, Petr
PY  - 2023
TI  - A unique case of Bloom syndrome with a combination of genetic hits: A lesson from trio-based exome sequencing: A case report
JF  - Molecular Medicine Reports
VL  - 27
IS  - 5
SP  - 1-9
EP  - 1-9
PB  - Spandidos Publications
SN  - 17912997
KW  - exome sequencing
KW  - BLM gene
KW  - Bloom syndrome
KW  - cancer-predisposing syndrome
KW  - copy-number neutral loss of heterozygosity
UR  - https://doi.org/10.3892/mmr.2023.12997
N2  - Pathogenic variants affecting the BLM gene are responsible for the manifestation of extremely rare cancer‑predisposing Bloom syndrome. The present study reports on a case of an infant with a congenital hypotrophy, short stature and abnormal facial appearance. Initially she was examined using a routine molecular diagnostic algorithm, including the cytogenetic analysis of her karyotype, microarray analysis and methylation‑specific MLPA, however, she remained undiagnosed on a molecular level. Therefore, she and her parents were enrolled in the project of trio‑based exome sequencing (ES) using Human Core Exome kit. She was revealed as a carrier of an extremely rare combination of causative sequence variants altering the BLM gene (NM_000057.4), c.1642C>T and c.2207_2212delinsTAGATTC in the compound heterozygosity, resulting in a diagnosis of Bloom syndrome. Simultaneously, a mosaic loss of heterozygosity of chromosome 11p was detected and then confirmed as a borderline imprinting center 1 hypermethylation on chromosome 11p15. The diagnosis of Bloom syndrome and mosaic copy‑number neutral loss of heterozygosity of chromosome 11p increases a lifetime risk to develop any types of malignancy. This case demonstrates the trio‑based ES as a complex approach for the molecular diagnostics of rare pediatric diseases.
ER  -

WAYHELOVÁ, Markéta, Vladimíra VALLOVÁ, Petr BROŽ, Aneta MIKULÁŠOVÁ, Dominika MACHÁČKOVÁ, Hana Dynková FILKOVÁ, Jan SMETANA, Alena TAKÁCSOVÁ, Renata GAILLYOVÁ and Petr KUGLÍK. A unique case of Bloom syndrome with a combination of genetic hits: A lesson from trio-based exome sequencing: A case report. \textit{Molecular Medicine Reports}. Spandidos Publications, 2023, vol.~27, No~5, p.~1-9. ISSN~1791-2997. Available from: https://dx.doi.org/10.3892/mmr.2023.12997.

Detailed Information on Publication Record