Significance Many patients with breast and ovarian cancer carry inherited cancer-predisposing mutations in BRCA1 . However, virtually no patients have two inherited mutations in BRCA1 because the DNA repair function of BRCA1 is essential for embryonic development. We discovered that patients with two nonsense mutations from a specific region of BRCA1 may survive as the result of naturally occurring alternative splicing that yields a short but partially functional BRCA1 protein. These patients are extremely rare, and are characterized by severe chromosomal fragility, congenital anomalies, and predisposition to childhood cancers.