FIGURE 1.

Schematic representation of predicted protein products encoded by the mutated PQBP1 gene in the Golabi-Ito-Hall syndrome (GIH S), the original family of Renpenning syndrome (R S), and the Hamel cerebropalatocardiac (H S) syndrome. The presence of the WW domain in PQBP1 was reconfirmed between amino acids 46 and 84. However, the C2 domain, another module that was proposed at the C-terminal region of PQBP1, could not be confirmed. Neither SMART nor PROSITE domain resource could detect the C2 domain in PQBP1. Therefore, this domain is considered as questionable (C2?). The region of PQBP1 that contains multiple, di-amino acid repeats, DR and ER, was demarcated between amino acids 104 and 176. A potential nuclear localization signal (N1), flanked by amino acids at positions 53–163, was predicted by the PredictNLS program (Columbia University, New York). The second potential nuclear localization signal (N2) was characterized previously and maps to amino acids 176–192 (3). In GIH syndrome, the transition mutation at the nucleotide 194 of PQBP1 (NCBI accession number NM_005710) causes missense substitution of Tyr to Cys at the amino acid position 65 in the conserved aromatic core of the WW domain. In Renpenning syndrome, the insertion of cytidine at the nucleotide position 641 caused a frameshift mutation that terminated the WT protein at amino acid position 213 and added new amino acids 214–225. In Hamel cerebropalatocardiac syndrome, a deletion of AG dinucleotide at position 461–462 caused a frameshift that resulted in the deletion of the putative nuclear localization signal (N1). Mutations are shown in italics (modified from Refs. 11 and 12).