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
. 2024 Mar 1;20(4):67.
doi: 10.3892/br.2024.1756. eCollection 2024 Apr.

Whole exome sequencing of a novel homozygous missense variant in PALB2 gene leading to Fanconi anaemia complementation group

Angham Abdulrhman Abdulkareem  1   2 , Bader H Shirah  3 , Hala Abubaker Bagabir  4 , Absarul Haque  5   6 , Muhammad Imran Naseer  1   6
Affiliations

Whole exome sequencing of a novel homozygous missense variant in PALB2 gene leading to Fanconi anaemia complementation group

Angham Abdulrhman Abdulkareem et al. Biomed Rep. .

Abstract

Partner and localiser of BRCA2 (PALB2), also known as FANCN, is a key tumour suppressor gene in maintaining genome integrity. Monoallelic mutations of PALB2 are associated with breast and overian cancers, while bi-allelic mutations cause Fanconi anaemia (FA). In the present study, whole exome sequencing (WES) identified a novel homozygous missense variant, NM_024675.3: c.3296C>G (p.Thr1099Arg) in PALB2 gene (OMIM: 610355) that caused FA with mild pulmonary valve stenosis and dysmorphic and atypical features, including lymphangiectasia, non-immune hydrops fetalis and right-sided pleural effusion in a preterm female baby. WES results were further validated by Sanger sequencing. WES improves the screening and detection of novel and causative genetic variants to improve management of disease. To the best of our knowledge, the present study is the first reported FA case in a Saudi family with phenotypic atypical FA features. The results support the role of PALB2 gene and pathogenic variants that may cause clinical presentation of FA. Furthermore, the present results may establish a disease database, providing a groundwork for understanding the key genomic regions to control diseases resulting from consanguinity.

Keywords: Fanconi anaemia; Saudi Arabia; homozygous; partner and localiser of BRCA2.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Pedigree of the family. IV-2 is the affected patient. * indicates subjects included in the present study.
Figure 2
Figure 2
PALB2 gene variants. Sanger sequencing showed that parents III-1 and III-2 were heterozygous carries with C/G on both alleles. Sibling IV-1 exhibited wild-type homozygous C/C, whereas IV-2 exhibited a novel homozygous missense variant c.3296C>G (p.Thr1099Arg) in PALB2 gene. Normal control samples were used from the local population. PALB2, Partner and localiser of BRCA2.
Figure 3
Figure 3
Conserved amino acid p.Thr1099Arg in PALB2 across species. PALB2, partner and localiser of BRCA2.
See this image and copyright information in PMC

References

    1. Park JY, Zhang F, Andreassen PR. PALB2: The hub of a network of tumor suppressors involved in DNA damage responses. Biochim Biophys Acta. 2014;1846:263–275. doi: 10.1016/j.bbcan.2014.06.003. - DOI - PMC - PubMed
    1. Simhadri S, Vincelli G, Huo Y, Misenko S, Foo TK, Ahlskog J, Sørensen CS, Oakley GG, Ganesan S, Bunting SF, Xia B. PALB2 connects BRCA1 and BRCA2 in the G2/M checkpoint response. Oncogene. 2019;38:1585–1596. doi: 10.1038/s41388-018-0535-2. - DOI - PMC - PubMed
    1. Hanenberg H, Andreassen PR. PALB2 (partner and localizer of BRCA2) Atlas Genet Cytogenet Oncol Haematol. 2018;22:484–290. doi: 10.4267/2042/69016. - DOI - PMC - PubMed
    1. Hamdan O, Nowak KM. Gene of the month: PALB2. J Clin Pathol. 2023;76:73–75. doi: 10.1136/jcp-2022-208461. - DOI - PubMed
    1. AlHarbi M, Mobark NA, AlJabarat WAR, ElBardis H, AlSolme E, Hamdan AB, AlFakeeh AH, AlMushawah F, AlHarthi F, AlSharm AA, et al. Investigating the prevalence of pathogenic variants in Saudi Arabian patients with familial cancer using a multigene next generation sequencing panel. Oncotarget. 2023;14:580–594. doi: 10.18632/oncotarget.28457. - DOI - PMC - PubMed

LinkOut - more resources