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

Angham Abdulrhman Abdulkareem; Bader H Shirah; Hala Abubaker Bagabir; Absarul Haque; Muhammad Imran Naseer

doi:10.3892/br.2024.1756

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

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

Authors

Angham Abdulrhman Abdulkareem^{1

2}, Bader H Shirah³, Hala Abubaker Bagabir⁴, Absarul Haque^{5

6}, Muhammad Imran Naseer^{1

6}

Affiliations

¹ Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
² Faculty of Science, Department of Biochemistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
³ Department of Neuroscience, King Faisal Specialist Hospital and Research Centre, Jeddah 11211, Saudi Arabia.
⁴ Department of Physiology, Faculty of Medicine, King Abdulaziz University, Rabigh 25732, Saudi Arabia.
⁵ King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁶ Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

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.

Grants and funding

Funding: The authors extend their appreciation to the King Salman Center for Disability Research for funding this work through Research Group no. KSRG-2023-024.