The importance of XPA in NER is illuminated by evidence demonstrating that of all XP phenotypes, patients deficient in XPA are most severely affected, XPA-deficient mice show a complete deficiency in NER, and XPA-deficient cells are most sensitive to UV irradiation [ 8– 11].
Furthermore, mutations Arg265Cys, Arg672Ter, Thr809Ter, which cause a complete respiratory deficiency, lead to a complete loss of functional mtDNA in the tested strains.
Recently, we showed the presence of large intragenic rearrangements of DPYD and a de novo interstitial deletion del(1)(p13.3p21.3) in five patients suffering from a complete DPD deficiency accompanied by a severe neurological disorder (van Kuilenburg et al. 2009).
Ninety percent of patients with anti-CFH antibodies have a complete deficiency of CFHR1 and CFHR3 associated with a homozygous deletion of CFHR1 and CFHR3, a polymorphism also observed in 4% of healthy individuals of European ancestry who do not develop anti-CFH antibodies.
Studies over the last several decades have demonstrated that a complete deficiency in factors mediating antibacterial response results in severe mycobacterial infections [4] [6].
No human repair-deficient disorders have been described so far suffering from a complete deficiency in BER, which may be taken to indicate that BER is essential for human development and survival.
Single knockout mice that lack each of RARs were not embryonic lethal and did not display the complete spectrum of vitamin A deficiency phenotype.
Another reported case of AIHA was reported in a patient who suffered from B cell chronic lymphocytic leukemia who was being treated with intermittent chemotherapy [ 15], while still another case was reported in a patient who had a complete congenital deficiency of IgA [ 16].
The disease is an excellent candidate for gene replacement therapy as the majority of mutations have been shown to lead to a complete deficiency of the secreted protein in the retinal structures.
To circumvent the embryonic lethality of a complete deficiency in insulin-like growth factor 1 (IGF-1), we generated mice homozygous for a site-specific insertional event that created a mutant IGF-1 allele (igf1m).
Dectin-1 is the main β-glucan receptor, and patients with a complete deficiency of either dectin-1 or its adaptor molecule CARD9 display persistent mucosal infections with Candida albicans.
