Table 1.
Characteristics of Autopsy Cases With Identified GBA Mutations
|
GBA Mutation/ Severitya |
cDNA Nucleotide Substitutionb |
Exon | Zygosity | Initial Clinical Presentation | Primary Pathological Diagnosis |
|
|---|---|---|---|---|---|---|
| Age, y | Symptom | |||||
| Null | ||||||
| 84insGG | c.84dupG | 2 | Heterozygous | 66 | Memory problems | DLB |
| Severe | ||||||
| H255Q | c.882T>G | 7 | Heterozygous | 55 | Behavior change | DLB |
| D409H | c.1342G>C | 9 | Heterozygous | 71 | Memory problems | DLB |
| L444P | c.1448T>C | 10 | Heterozygous | 55 | Parkinsonism | DLB |
| R463C | c.1504C>T | 10 | Heterozygous | NA | Memory problems | DLB |
| Mild | ||||||
| N370S | c.1226A>G | 9 | Heterozygous | 68 | Memory problems | LBV-AD |
| N370S | c.1226A>G | 9 | Heterozygous | 62 | Parkinsonism | DLB |
| N370S | c.1226A>G | 9 | Heterozygous | 58 | Parkinsonism | DLB |
| N370S | c.1226A>G | 9 | Heterozygous | 74 | Parkinsonism | DLB |
| N370S | c.1226A>G | 9 | Heterozygous | 69 | Parkinsonism | DLB |
| N370S | c.1226A>G | 9 | Heterozygous | NA | NA | DLB |
| N370S | c.1226A>G | 9 | Heterozygous | 54 | Parkinsonism | DLB |
| N370S | c.1226A>G | 9 | Heterozygous | 55 | Memory problems | DLB |
| N370S | c.1226A>G | 9 | Heterozygous | 69 | Memory problems | LBV-AD |
| N370S | c.1226A>G | 9 | Homozygous | NA | Memory problems | AD |
| R496H | c.1604G>A | 11 | Heterozygous | 74 | Parkinsonism | DLB |
| Unknown | ||||||
| g.1444 A>G | g.1444 A>G | −15 of ATG start codon |
Heterozygous | 74 | Memory problems | AD |
| P171P | c.630C>T | 6 | Heterozygous | 57 | Language problems | AD |
| W184R | c.667T>C | 6 | Heterozygous | 53 | Parkinsonism | DLB |
| E326K | c.1093G>A | 8 | Heterozygous | 41 | Parkinsonism | DLB |
| E326K | c.1093G>A | 8 | Heterozygous | 58 | Parkinsonism | DLB |
| E326K | c.1093G>A | 8 | Heterozygous | 58 | Parkinsonism | PD |
| E326K | c.1093G>A | 8 | Heterozygous | 67 | Parkinsonism | LBV-AD |
| E326K + N188R + S196P +V191G |
c.1093G>A, c.680A>G + c.681T>G, C.703T>C, c.689T>G |
8, 6, 6, 6 | Compound heterozygous |
65 | Hallucinations | DLB |
| T369M | c.1223C>T | 8 | Heterozygous | 69 | Parkinsonism | DLB |
| T369M | c.1223C>T | 8 | Heterozygous | 72 | Memory problems | LBV-AD |
| T369M | c.1223C>T | 8 | Heterozygous | NA | NA | Normal brain |
| T369M | c.1223C>T | 8 | Heterozygous | 53 | Memory problems | AD |
| T369M | c.1223C>T | 8 | Heterozygous | 70 | Depression | AD |
| T369M | c.1223C>T | 8 | Heterozygous | 69 | Personality change | DLB |
| T369M | c.1223C>T | 8 | Homozygous | 67 | Performance change | DLB |
| T369M | c.1223C>T | 8 | Heterozygous | NA | Memory problems | DLB |
| E388K | c.1279G>A | 9 | Heterozygous | 55 | Memory problems | LBV-AD |
| G389V | c.1283G>T | 9 | Heterozygous | 58 | Performance change | AD |
Abbreviations: AD, Alzheimer disease; cDNA, complementary DNA; DLB, dementia with Lewy bodies; LBV-AD, Lewy body variant of Alzheimer disease; NA, not available; PD, Parkinson disease.
a
Mutations are classified as having null, severe, mild, and unknown effect on the expected clinical phenotype according to Beutler et al.24
b
Genomic nucleotide position is based on the accession file GenBank J03059.1, and GBA cDNA nucleotides are numbered according to the GenBank sequence NM_000157.2.