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.

Základní údaje

Originální název

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

Autoři

WAYHELOVÁ, Markéta; Vladimíra VALLOVÁ; Petr BROŽ; Aneta MIKULÁŠOVÁ; Dominika MACHÁČKOVÁ; Hana Dynková FILKOVÁ; Jan SMETANA; Alena TAKÁCSOVÁ; Renata GAILLYOVÁ a Petr KUGLÍK

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10603 Genetics and heredity

Stát vydavatele

Řecko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.400

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/23:00134634

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

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

Štítky

14314010, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 23. 5. 2023 12:39, Mgr. Marie Novosadová Šípková, DiS.

Anotace

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.

Návaznosti

NU20-07-00145, projekt VaV

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

Investor: Ministerstvo zdravotnictví ČR, Úloha patogenních genetických variant detekovaných pomocí exomového sekvenování v etiologii dětských neurovývojových onemocnění, Podprogram 1 - standardní

Citovat

WAYHELOVÁ, Markéta; Vladimíra VALLOVÁ; Petr BROŽ; Aneta MIKULÁŠOVÁ; Dominika MACHÁČKOVÁ; Hana Dynková FILKOVÁ; Jan SMETANA; Alena TAKÁCSOVÁ; Renata GAILLYOVÁ a 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, roč. 27, č. 5, s. 1-9. ISSN 1791-2997. Dostupné z: https://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 = {https://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 a 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, roč.~27, č.~5, s.~1-9. ISSN~1791-2997. Dostupné z: https://doi.org/10.3892/mmr.2023.12997.

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