Knockout models of the gene LIG4, located in human chromosome 13 and consisting of a single long exon, are lethal to mouse embryos because of massive neuronal apoptosis (4); all known human mutations are thus hypomorphic and result in a wide clinical spectrum, ranging from normal to severely compromised immune system with microcephaly, growth failure, facial dysmorphism, mental retardation, hypogonadism, progressive bone marrow failure, and leukemia or lymphoma. This evidence concerns the gene LIG4 and microcephaly.