We demonstrate that both WT PHOX2B and the neuroblastoma-associated R100L missense and the CCHS-associated alanine expansion variants induce nuclear translocation of HPCAL1 in a Ca(2+)-independent manner, while the neuroblastoma-associated 676delG frameshift and K155X truncation mutants impair subcellular localization of HPCAL1, causing it to remain in the cytoplasm.
We identified two mutations, 600delC, a frameshift mutation in an individual with isolated, unifocal NB and G197D, a missense mutation that was present in a family with multiple individuals with NB but no evidence of autonomic dysfunction.