Table 9.4: Sequence variations in the PHYH gene associated with adult Refsum's disease
| Nucleotide change | Exon | Predicted effect | Number of families affected | Frequency (%) | ||
|---|---|---|---|---|---|---|
| Homozygote | Heterozygote | |||||
| Missense | ||||||
| 85 | C—>T | 2 | P29S | 1 | 7 | 6.7 |
| 120 | C—>T | 3 | Q40X | 4 | 3.3 | |
| 247 | A—>T | 4 | N83Y | 1 | 1.0 | |
| 517 | C—>T | 6 | P173S | 1 | 1.6 | |
| 524 | A—>G | 6 | H175R | 1 | 1.0 | |
| 526 | C—>A | 6 | Q176K | 1 | 1.0 | |
| 526 | C—>T | 6 | Q176X | 1 | 1.0 | |
| 530 | A—>G | 6 | D177G | 2 | 2 | 5.0 |
| 577 | T—>C | 6 | W193R | 1 | 1 | 2.5 |
| 589 | G—>C | 6 | E197Q | 1 | 1.0 | |
| 595 | G—>C | 6 | I199F | 1 | 1.0 | |
| 610 | G—>A | 6 | G204S | 1 | 1 | 2.5 |
| 636 | A—>G* | 6 | no change | 2 | 1 | 4.0 |
| 658 | C—>T | 6 | H220Y | 4 | 3.3 | |
| 734 | G—>A** | 7 | R245Q | 2 | 2 | 5.0 |
| 770 | T—>C | 7 | F257S | 2 | 1 | 4.0 |
| 805 | A—>C | 7 | N269H | 1 | 1.0 | |
| 823 | G—>A | 7 | R275W | 2 | 4 | 6.7 |
| 824 | G—>A | 7 | R275Q | 1 | 1 | 2.5 |
| Deletion | ||||||
| 164 | del T | 3 | L55fsX12 | 2 | 4 | 6.7 |
| 258-265 | del | 4 | E86fsX26 | 3 | 1 | 5.8 |
| 375-376 | del GG | 4 | E126fsX1 | 1 | 1.7 | |
| 457 | del G | 7 | G228fsX2 | 1 | 1.7 | |
| Insertion | ||||||
| 576-577 | ins GCC | 6 | 192_193insA | 1 | 1.7 | |
| 683-684 | ins G | 7 | G228fsX2 | 2 | 1.7 | |
| Splice site | ||||||
| 135-2 | A—>G | (-3) | Y46_R82 (r135-245 del) | 2 | 5 | 7.5 |
| 135-1 | G—>C | (-3) | Y46_R82 (r135-245 del) | 2 | 1.7 | |
| 497-2 | A—>G | (-6) | A166fsX3 (r497_678 del) | 3 | 1 | 5.8 |
| 678+2 | T—>G | (-6) | A166fsX3 (r497_678 del) | 1 | 1.7 | |
| 678+5 | G—>T | (-6) | A166fsX3 (r497_678 del) | 1 | 5 | 5.8 |
| 679-1 | G—>T | (-6) | A166fsX3 (r497_678 del) | 1 | 1.7 | |
Modified and updated (April 2006) after Jansen GA et
al; Human Mutation (2004) 23 :209-218 table 1.
Numbering is from the first ATGA codon (position 60) according to cDNA sequence
at Genbank accession number NM_006214.2. For PHYH gene structure see
Jansen et al (2000) and Genbank
PubMed reference AF242379-AF242386.
* This variant is found in 10% of the population.
** This co-segregated with 530 A—>G (D177G) and when expressed has normal
enzyme activity. It may be a normal variant.