Figure 2

Nucleotide sequence analysis of LIPA. The nucleotide sequences, codon numbers, single letter amino acid codes for the deduced protein sequence are shown in each panel. Panel A shows normal LIPA genomic sequence above and the sequence from the proband's genomic DNA below. The inserted nucleotide is indicated by the arrow and the shifted reading frame is suggested by the presence of two peaks at each position following the insertion. Panel B shows normal LIPA genomic sequence above and the sequence from the proband's genomic DNA below, with abnormal sequence italicized. The single base nonsense mutation is indicated by the arrow. Panel C shows normal LIPA cDNA sequence from a single copy cloned source derived from a normal individual, spanning part of exon 7, all of exon 8 and then part of exon 9. The lower part of the panel shows the cDNA sequence for one of the proband's alleles, in which exon 8 has been deleted in frame. This confirms that the mutation at the intron-exon boundary of exon 8 affected RNA splicing.