Pathogenic FANCC Variants are Associated with Accessory Breasts in a Sub-Saharan African Multiplex Family

Accessory breasts denote the formation of extra breast tissue along the milk line, being more prevalent among Black and Asian populations, affecting both genders. This study aimed to determine the genetic aetiology of accessory breasts in a multiplex family, where all female siblings presented with bilateral accessory breasts. The study also ascertained secondary findings (SFs) that may impact the health of the family members. Clinical data and saliva samples were obtained from all family members. Ultrasound and histopathology confirmed the diagnosis. Whole-exome sequencing was conducted on DNA samples obtained from the saliva, with variant calling conducted utilizing Sentieon workflow. Variant classification was based on American College of Medical Genetics and Genomics guidelines. After segregation analysis, 12 candidate genes emerged. Among these, PRSS50 and FANCC emerged as top candidates, being implicated in breast diseases. However, two variants in FANCC (c.360del; p.His120GlnfsTer24 and c.355_358del; p.Ser119IlefsTer24) were selected as the most probable causal variants because of the role of this gene in familial hereditary breast and ovarian cancer syndromes. The remaining ten genes were reported as potentially accounting for co-occurring conditions segregating with accessory breasts. Reported SFs involve TTR and RYR1. In conclusion, pathogenic variants in FANCC are causal for familial accessory breasts.