Table 4.
Reported PHKA2 mutations in Asian patients with glycogen storage disease (GSD) type IX
| Ethnicity | Exon number | Nucleotide change | Amino acid change | Mutation type | Reference |
|---|---|---|---|---|---|
| Point mutation | |||||
| Chinese | 2 | c.136delG | p.Asp46Ilefs*37 | Frameshift | [31] |
| Japanese | 4 | c.346 T > G | p.Tyr116Asp | Missense | [32] |
| Japanese | 6 | c.578G > T | p.Gly193Val | Missense | [32] |
| Japanese | 9 | c.883C > T | p.Arg295Cys | Missense | [25] |
| Korean | 9 | c.884G > Aa | p.Arg295His | Missense | [8], This study |
| Japanese | 15 | c.1489C > T | p.Arg497* | Nonsense | [25] |
| Japanese | 16 | c.1697A > T | p.Ile566Asn | Missense | [33] |
| Japanese | 32 | c.3505C > T | p.Gln1169* | Nonsense | [25] |
| Japanese, Chineseb | 33 | c.3614C > T | p.Pro1205Leu | Missense | [22, 24, 32, 34] |
| Splicing mutation | |||||
| Japanese | 2 | c.79-1G > T | Exon 2 skipping | Splicing | [25] |
| Korean | IVS5 | c.537 + 5G > A | ?c | Splicing | [6], This study |
| Japanese | 25 | c.2675A > G | Exon 25 skipping | Splicing | [32] |
| Chinese | 30 | c.3112-1G > A | Exon 30 skipping | Splicing | [31] |
| Deletion mutation | |||||
| Korean | 30 | c.3210_3212delGAG | p.Arg1072del | Small deletion | [18, 19], This study |
| Korean | 8 | Exon 8 deletion | Gross deletion | [13], This study | |
| Korean | 18–33 | Exon 18–33 deletions | Gross deletion | This study | |
| Japanese | 20–26 | Exon 20–26 deletions | Gross deletion | [29] | |
| Korean | 27–33 | Exon 27–33 deletions | Gross deletion | [6], This study | |
aThis mutation has been reported previously in two patients with GSD IX and is predicted to affect protein function by in silico analyses (SIFT and PolyPhen-2) and to affect splicing, potentially through activation of an exonic cryptic donor site, by both Human Splice Finder software and by a machine-learning technique that scores how strongly genetic variants affect RNA splicing [27]
bThis mutation has been reported as a founder mutation in the Dutch population
cAlthough in vitro analysis for the splicing effect of c.537 + 5G > A was not performed, in vivo results confirming phosphorylase b kinase deficiency have been reported to constitute a pathogenic mutation in a patient with GSD IX in previous literature. This mutation was predicted to affect splicing, potentially through alteration of the wild-type donor site