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

Partner and localiser of BRCA2 ( ), also known as , is a key tumour suppressor gene in maintaining genome integrity. Monoallelic mutations of 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 2 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 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.