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.

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