current current no assertion criteria provided Pathogenic germline human not provided literature only In 2 sibs with Wolman disease (278000) from a consanguineous family, Aslanidis et al. (1996) detected homozygosity for a G-to-A mutation at position +1 of the splice donor site following exon 8 of the LIPA gene. Both children died within the first year of life. The parents, who were heterozygous for the mutation, had reduced enzymatic activity, while no enzymatic activity was detectable in fibroblasts from the affected children. Although the same donor splice site is involved as in the mutation reported in CESD (934G-A, 613497.0002), the nucleotide at position +1 was changed in the Wolman disease mutation while the nucleotide at position -1 was changed in the CESD mutation. Both mutations result in deletion of the same 24 amino acids (exon 8), but the effects are dramatically different: the -1 mutation allowed some correct splicing (3% of total LIPA RNA), but the +1 splice site mutation, which affects one of the invariable nucleotides of the splice consensus sequences, permits no correct splicing. Aslanidis et al. (1996) suggested that the residual activity in CESD patients compared to Wolman patients may result either from a partially active enzyme with the internal deletion of 24 amino acids (skipping of exon 8) or from the production of low amounts of the full size of the protein due to inefficient exon exclusion from the mutated allele. 8617513 NM_000235.4(LIPA):c.894+1G>A NM_001288979.1:c.546+1G>A NM_000235.4:c.894+1G>A NM_001127605.3:c.894+1G>A NG_008194.1:g.34394G>A NC_000010.11:g.89222510C>T NC_000010.10:g.90982267C>T NM_000235.3:c.894+1G>A splice donor variant splice donor variant splice donor variant IVS8, G-A, +1 10q23.31 lipase A, lysosomal acid type LIPA ClinGen staff contributed the HGVS expression for this variant. NM_000235.4(LIPA):c.894+1G>A Wolman disease current no assertion criteria provided Pathogenic germline human not provided literature only In 2 sibs with Wolman disease (278000) from a consanguineous family, Aslanidis et al. (1996) detected homozygosity for a G-to-A mutation at position +1 of the splice donor site following exon 8 of the LIPA gene. Both children died within the first year of life. The parents, who were heterozygous for the mutation, had reduced enzymatic activity, while no enzymatic activity was detectable in fibroblasts from the affected children. Although the same donor splice site is involved as in the mutation reported in CESD (934G-A, 613497.0002), the nucleotide at position +1 was changed in the Wolman disease mutation while the nucleotide at position -1 was changed in the CESD mutation. Both mutations result in deletion of the same 24 amino acids (exon 8), but the effects are dramatically different: the -1 mutation allowed some correct splicing (3% of total LIPA RNA), but the +1 splice site mutation, which affects one of the invariable nucleotides of the splice consensus sequences, permits no correct splicing. Aslanidis et al. (1996) suggested that the residual activity in CESD patients compared to Wolman patients may result either from a partially active enzyme with the internal deletion of 24 amino acids (skipping of exon 8) or from the production of low amounts of the full size of the protein due to inefficient exon exclusion from the mutated allele. 8617513 LIPA, IVS8, G-A, +1 IVS8, G-A, +1 LIPA WOLMAN DISEASE